AZN Astrazeneca PLC

56.45
+0.51  (+1%)
Previous Close 55.94
Open 56.76
52 Week Low 36.15
52 Week High 64.94
Market Cap $148,157,288,330
Shares 2,624,575,524
Float 2,624,575,524
Enterprise Value $161,593,413,340
Volume 2,931,338
Av. Daily Volume 7,002,439
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Upcoming Catalysts

Drug Stage Catalyst Date
AZD1222 (ChAdOx1 nCoV-19)
COVID-19 vaccine
Phase 3
Phase 3
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Brilinta (THALES)
Acute ischaemic stroke
PDUFA priority review
PDUFA priority review
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Roxadustat
Anaemia in Chronic Kidney Disease
PDUFA
PDUFA
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MEDI0457
HPV-associated squamous cell carcinoma of the head & neck (SCCHN)
Phase 1/2
Phase 1/2
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Imfinzi - PACIFIC-2
Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
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Tezepelumab - NAVIGATOR
Asthma
Phase 3
Phase 3
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Fasenra OSTRO
Nasal polyps
Phase 3
Phase 3
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Imfinzi + tremelimumab - HIMALAYA
Hepatocellular carcinoma (HCC)
Phase 3
Phase 3
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Imfinzi (PEARL)
Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
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Lynparza - OlympiA
HER2-negative breast cancer
Phase 3
Phase 3
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Durvalumab +/- tremelimumab (KESTREL)
Head & neck cancer
Phase 3
Phase 3
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Imfinzi (PACIFIC-5)
Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
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Roxadustat
Myelodysplastic syndromes (MDS)
Phase 3
Phase 3
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Brazikumab
Crohn's disease
Phase 3
Phase 3
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Brazikumab
Ulcerative colitis
Phase 2/3
Phase 2/3
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Imfinzi + tremelimumab (POSEIDON)
Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
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Imfinzi
Muscle-invasive bladder cancer
Phase 3
Phase 3
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Trastuzumab deruxtecan DESTINY-Breast02
Third line HER2+ breast cancer
Phase 3
Phase 3
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Farxiga (Deliver)
Chronic Heart Failure (CHF), preserved ejection fraction (HFpEF)
Phase 3
Phase 3
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Lynparza - PROpel
Castration-resistant prostate cancer -first line
Phase 3
Phase 3
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Trastuzumab deruxtecan - DESTINY-Breast04
HER low breast cancer
Phase 3
Phase 3
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Imfinzi TOPAZ-1
Biliary-tract cancer
Phase 3
Phase 3
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Trastuzumab deruxtecan - DESTINY-Breast03
Second line HER2+ breast cancer
Phase 3
Phase 3
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Durvalumab Plus Danvatirsen
Refractory head and neck cancer
Phase 1/2
Phase 1/2
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PT027
Asthma
Phase 3
Phase 3
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Durvalumab - EMERALD-1
Locoregional Hepatocellular carcinoma (HCC)
Phase 3
Phase 3
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Imfinzi
Non-muscle invasive bladder cancer
Phase 3
Phase 3
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Imfinzi - AEGEAN
Neoadjuvant Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
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Fasenra
hypereosinophilic syndrome (HES)
Phase 3
Phase 3
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Fasenra
Chronic obstructive pulmonary disease (COPD) and peripheral blood eosinophils
Phase 3
Phase 3
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Durvalumab (ADJUVANT)
Adjuvant Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
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Fasenra MANDARA
Eosinophilic granulomatosis with polyangiitis
Phase 3
Phase 3
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Imfinzi
Locoregional Hepatocellular carcinoma (HCC)
Phase 3
Phase 3
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Fasenra MESSINA
Eosinophilic oesophagitis
Phase 3
Phase 3
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Imfinzi + tremelimumab (NILE)
Bladder cancer
Phase 3
Phase 3
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Imfinzi CALLA
Cervical cancer
Phase 3
Phase 3
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Imfinzi DuO-O
Ovarian cancer
Phase 3
Phase 3
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Durvalumab - ADRIATIC
Small cell lung cancer (SCLC) limited disease
Phase 3
Phase 3
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Fasenra
Asthma
Phase 3
Phase 3
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Drug Pipeline

Drug Stage Notes
Durvalumab +/- tremelimumab (NEPTUNE)
Lung cancer
Phase 3
Phase 3
Phase 3 data released August 21, 2019 did not meet primary endpoint.
Tagrisso (ADAURA)
Non-small Cell Lung Carcinoma
Phase 3
Phase 3
Phase 3 data released May 28, 2020 noted a reduction in the risk of disease recurrence or death by 83%.
Breztri - (ETHOS)
Chronic obstructive pulmonary disease (COPD)
Approved
Approved
FDA approval announced July 24, 2020.
Durvalumab +/- tremelimumab (DANUBE)
Bladder cancer
Phase 3
Phase 3
Phase 3 data released March 6, 2020 did not meet primary endpoint.
Brilinta (THEMIS)
Type 2 Diabetes / coronary artery disease (CAD)
Approved
Approved
FDA approval announced June 1, 2020.
Lynparza
Castration-Resistant Prostate Cancer
Approved
Approved
FDA Approval announced May 19, 2020.
Lynparza + Avastin- PAOLA-1
First-line ovarian cancer
Approved
Approved
FDA Approval announced May 8, 2020.
Farxiga (Dapa-HF)
Heart failure
Approved
Approved
FDA Approval announced May 5, 2020.
Farxiga (Dapa-CKD)
Chronic Kidney Disease
Phase 3
Phase 3
Phase 3 trial stopped early due to overwhelming efficacy.
Selumetinib
Neurofibromatosis type 1 plexiform neurofibromas
Approved
Approved
FDA Approval announced April 13, 2020.
Imfinzi + tremelimumab (CASPIAN)
Small cell lung cancer (SCLC)
Approved
Approved
FDA approval announced March 30, 2020.
Lynparza + cediranib
Ovarian cancer
Phase 3
Phase 3
Phase 3 trial did not meet primary endpoint - March 12, 2020.
Epanova
Hypertriglyceridaemia CVOT
Phase 3
Phase 3
Phase 3 trial to be discontinued due to low likelihood of demonstrating a benefit - January 13, 2020.
Trastuzumab deruxtecan - DESTINY-Gastric01
Gastric cancer
Phase 2
Phase 2
Phase 2 data trial met primary endpoint.
Lynparza (POLO)
Pancreatic cancer
Approved
Approved
FDA Approval announced December 30, 2019.
Enhertu (trastuzumab deruxtecan)
Third line HER2+ breast cancer
Approved
Approved
FDA Approval announced December 20, 2019.
Calquence
Chronic lymphocytic leukaemia
Approved
Approved
FDA Approval announced November 21, 2019.
Anifrolumab
Lupus
Phase 3
Phase 3
Phase 3 TULIP 1 data released August 31, 2018. Primary endpoint not met. TULIP 2 data released August 29, 2019 did meet primary endpoint.
Farxiga - DECLARE
Heart failure in patients with type-2 diabetes
Approved
Approved
FDA Approval announced October 21, 2019.
PT010
Chronic obstructive pulmonary disease (COPD)
CRL
CRL
CRL announced October 1, 2019.
Tagrisso - FLAURA
Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
Phase 3 final OS data released August 9, 2019. Endpoint met. Presentation at ESMO September 2019 noted OS of 38.6 months versus 31.8 months for comparator arm; PFS HR 0.48.
Calquence
Relapsed/refractory chronic lymphocytic leukaemia
Phase 3
Phase 3
Phase 3 positive interim data released May 7, 2019. Trial to be stopped early.
Selumetinib - ASTRA
Thyroid cancer
Phase 3
Phase 3
Phase 3 trial did not meet primary endpoint - noted July 26, 2018.
Farxiga (Depict)
Type 1 diabetes
CRL
CRL
CRL issued for sNDA announced July 15, 2019.
Durvalumab +/- tremelimumab (EAGLE)
Head & neck cancer
Phase 3
Phase 3
Phase 3 data released December 7, 2018 - primary endpoints not met.
Durvalumab +/- tremelimumab (MYSTIC)
Lung cancer
Phase 3
Phase 3
Phase 3 data released July 27, 2017 - primary endpoint (PFS) not met. Overall survival data also did not meet primary endpoint - November 16, 2018.
Lanabecestat (AZD3293) - AMARANTH
Early Alzheimer's disease
Phase 3
Phase 3
Announced discontinuation of trial due to futility - June 12, 2018.
Lynparza - SOLO 3
Third-line ovarian cancer
Phase 3
Phase 3
Phase 3 data met primary and secondary endpoints. ORR; 72.2% vs 51.4% for chemotherapy. PFS 13.4 months vs 9.2 months for chemo arm (HR 0.62).
Qternmet XR (dapagliflozin, saxagliptin and metformin hydrochloride)
Type 2 diabetes
Approved
Approved
FDA approval announced May 3, 2019.
Lynparza - SOLO 1
First-line ovarian cancer following platinum-based chemotherapy
Approved
Approved
FDA Approval announced December 19, 2018.
Moxetumomab
Cancer - leukaemia
Approved
Approved
FDA approval announced September 13, 2018.
Durvalumab (PACIFIC)
Lung cancer
Approved
Approved
Approval announced February 19, 2018.
Benralizumab - TERRANOVA
COPD
Phase 3
Phase 3
Phase 3 data released May 30, 2018. Primary endpoint not met.
Lokelma (ZS-9)
Hyperkalaemia
Approved
Approved
Second CRL issued March 17, 2017. Approval announced May 18, 2018.
Fasenra (benralizumab) - GALATHEA
Chronic obstructive pulmonary disease (COPD)
Phase 3
Phase 3
Phase 3 trial did not meet primary endpoint - noted May 11, 2018.
Urothelial carcinoma - Bladder cancer
Bladder cancer
Approved
Approved
BLA acceptance announced December 9, 2017. PDUFA under priority review. Approval announced May 1, 2017.
Durvalumab +/- tremelimumab (ARCTIC)
Non-small cell lung cancer (NSCLC)
Phase 3
Phase 3
Phase 3 data released April 24, 2018 - primary endpoints not met.
Benralizumab
Severe, uncontrolled asthma
Approved
Approved
Approval announced November 14, 2017.
Acalabrutinib
Relapsed or Refractory Mantle Cell Lymphoma
Approved
Approved
Priority Review announced August 2, 2017. Approval announced October 31, 2017.
Saxagliptin and dapagliflozin
Type-2 diabetes
Approved
Approved
Approval announced February 28, 2017.
Bydureon
Type 2 Diabetes
Phase 3
Phase 3
Phase 3 Cardiovascular Outcome trial data released September 14, 2017 - primary efficacy objective of a superior reduction in MACE missed statistical significance (p=0.061).
Lynparza - SOLO 2
Second-line ovarian cancer
Approved
Approved
Approval announced August 17, 2017.
Lynparza
Breast cancer
Approved
Approved
Phase 3 data released February 17, 2016 - primary endpoint met. Late breaker at ASCO June 4, 2017 showed HR of 0.58 (42% reduction of risk of disease progression or death). Approval announced January 12, 2018.
Tralokinumab (STRATOS1)
Severe, uncontrolled asthma
Phase 3
Phase 3
Phase 3 trial did not meet primary endpoint - May 10, 2017.
Tagrisso
Epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC)
Approved
Approved
Approval announced March 31, 2017.
Tralokinumab (STRATOS2)
Severe, uncontrolled asthma
Phase 3
Phase 3
Phase 3 data released November 1, 2017 - primary endpoint not met.
Faslodex (fulvestrant)
Monotherapy for expanded use in women with HR+, HER2- advanced breast cancer
Approved
Approved
Expanded approval announced August 28, 2017.

Latest News

  1. LYNPARZA is the only PARP inhibitor to demonstrate overall survival in metastatic castration-resistant prostate cancer

    AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced final results from the Phase III PROfound trial that showed LYNPARZA (olaparib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus enzalutamide or abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 or ATM gene mutations, a subpopulation of homologous recombination repair (HRR) gene mutations. Patients had progressed on prior treatment with new hormonal agent (NHA) treatments (i.e., enzalutamide and abiraterone).

    Prostate cancer…

    LYNPARZA is the only PARP inhibitor to demonstrate overall survival in metastatic castration-resistant prostate cancer

    AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced final results from the Phase III PROfound trial that showed LYNPARZA (olaparib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus enzalutamide or abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 or ATM gene mutations, a subpopulation of homologous recombination repair (HRR) gene mutations. Patients had progressed on prior treatment with new hormonal agent (NHA) treatments (i.e., enzalutamide and abiraterone).

    Prostate cancer is the second-most common type of cancer in men. An estimated 191,930 men in the United States will be diagnosed with prostate cancer in 2020. Approximately 20-30% of men with mCRPC have an HRR gene mutation.

    In the key secondary endpoint of OS, LYNPARZA reduced the risk of death in patients with BRCA1, BRCA2, ATM mutations by 31% versus enzalutamide or abiraterone (based on a hazard ratio [HR] of 0.69; 95% confidence interval [CI] 0.50-0.97; p=0.0175). Median OS was 19.1 months for LYNPARZA versus 14.7 months for enzalutamide or abiraterone, despite 66% of men on NHA treatments had crossed over to receive treatment with LYNPARZA following disease progression.

    An exploratory analysis also showed a non-statistically significant improvement in OS in the overall trial population of men with HRR gene mutations (BRCA1/2, ATM, CDK12 and 11 other HRRm genes), reducing the risk of death by 21% with LYNPARZA versus enzalutamide or abiraterone (based on a HR of 0.79; 95% CI 0.61-1.03). Median OS was 17.3 months versus 14.0 months for enzalutamide or abiraterone.

    Johann de Bono, one of the principal investigators of the PROfound trial, Head of Drug Development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said: "LYNPARZA has demonstrated significant clinical benefit across key endpoints in PROfound and the final overall survival results reinforce its potential to change the treatment standard for certain men with metastatic castration-resistant prostate cancer. The PROfound trial shows that LYNPARZA can play an important role in this new era of precision medicine in prostate cancer, bringing a targeted therapy at a molecular level to patients with a historically poor prognosis and few treatment options."

    José Baselga, Executive Vice President, Oncology R&D, said: "These results help to transform the treatment landscape for certain men with metastatic castration-resistant prostate cancer, where overall survival has been very difficult to achieve. LYNPARZA is the only PARP inhibitor to demonstrate overall survival versus enzalutamide or abiraterone for men with BRCA or ATM mutations. We look forward to continuing to bring LYNPARZA to these patients around the world."

    Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck, said: "The PROfound trial is the first positive Phase III trial using molecular biomarker testing to help identify treatment options for certain men with metastatic castration-resistant prostate cancer. These results further underpin the importance of genomic testing for HRR gene mutations to identify this at-risk patient population and help physicians make treatment decisions. These results demonstrate the potential of LYNPARZA for metastatic castration-resistant prostate cancer patients with certain HRR mutations."

    Final OS results from the PROfound trial were presented on Sunday, September 20 during the Presidential Symposium at the 2020 European Society of Medical Oncology virtual congress, and published simultaneously in The New England Journal of Medicine.

    Summary of OS results

    OS data cut-off date was March 20, 2020

     

    Men with BRCA1/2 and

    ATM mutations

    Overall population

    (HRRm - BRCA1/2, ATM

    and 12 other genes)

    LYNPARZA

    n=162

    enzalutamide

    and

    abiraterone

    n=83

    LYNPARZA

    n=256

    enzalutamide

    and

    abiraterone

    n=131

    Median, months

    19.1

    14.7

    17.3

    14.0

    Hazard ratio (95% CI)

    0.69 (0.50, 0.97)

    0.79 (0.61, 1.03)

    p-value

    0.0175

    n/a

    Kaplan-Meier estimates of OS

    6-months (%)

    91

    84

    92

    83

    12-months (%)

    73

    61

    67

    56

    18-months (%)

    54

    42

    47

    39

    Median follow-up, months

    21.9

    21.0

    20.7

    20.5

    The most common adverse events (AEs) ≥20% were anemia (50%), nausea (43%), fatigue/asthenia (42%), decreased appetite (31%), diarrhea (21%) and vomiting (20%). The most common ≥ grade 3 AEs were anemia (23%), nausea (2%), fatigue/asthenia (3%), decreased appetite (2%) and diarrhea (1%). Twenty percent of patients on LYNPARZA discontinued treatment due to AEs.

    The Phase III PROfound trial had met its primary endpoint in August 2019, showing LYNPARZA significantly improved radiographic progression-free survival (rPFS) in men with BRCA1/2 or ATM genes, and had met a key secondary endpoint of rPFS in the overall HRRm population, which formed the basis of the US approval in May 2020. Regulatory reviews are ongoing in the EU and other countries.

    AstraZeneca and Merck are exploring additional trials in metastatic prostate cancer including the ongoing Phase III PROpel trial testing LYNPARZA as a 1st-line medicine for patients with mCRPC in combination with abiraterone versus abiraterone alone. Data is anticipated in the second half of 2021.

    IMPORTANT SAFETY INFORMATION

    CONTRAINDICATIONS

    There are no contraindications for LYNPARZA.

    WARNINGS AND PRECAUTIONS

    Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

    Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

    If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

    Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

    Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

    Females

    Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

    Males

    Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

    Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

    ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

    ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

    Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

    In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

    ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

    Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

    ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

    ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

    ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

    ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

    DRUG INTERACTIONS

    Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

    CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

    CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

    USE IN SPECIFIC POPULATIONS

    Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

    Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

    Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

    Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

    INDICATIONS

    LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

    First-Line Maintenance BRCAm Advanced Ovarian Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

    In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

    • a deleterious or suspected deleterious BRCA mutation, and/or
    • genomic instability

    Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Maintenance Recurrent Ovarian Cancer

    For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

    Advanced gBRCAm Ovarian Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    gBRCAm, HER2-Negative Metastatic Breast Cancer

    For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

    About Metastatic Castration-Resistant Prostate Cancer (mCRPC)

    Prostate cancer is the second-most common cancer in men. An estimated 191,930 men in the United States will be diagnosed with prostate cancer in 2020. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis. Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Despite advances in treatment for men with mCRPC, five-year survival is low and extending survival remains a key goal.

    About Homologous Recombination Repair (HRR) Gene Mutations

    HRR genes allow for accurate repair of damaged DNA in normal cells. HRR deficiency (HRD) means the DNA damage cannot be repaired, and can result in normal cell death. This is different in cancer cells, where a mutation in HRR pathways leads to abnormal cell growth and therefore cancer. HRD is a well-documented target for PARP inhibitors, such as LYNPARZA. PARP inhibitors block a rescue DNA damage repair mechanism by trapping PARP bound to DNA single-strand breaks which leads to replication fork stalling causing their collapse and the generation of DNA double-strand breaks, which in turn lead to cancer cell death.

    About PROfound

    PROfound is a prospective, multi-center, randomized, open-label, Phase III trial testing the efficacy and safety of LYNPARZA versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment with NHA treatments (abiraterone or enzalutamide) and have a qualifying tumor mutation in BRCA1/2, ATM or one of 12 other genes involved in the HRR pathway.

    The trial was designed to analyze patients with HRRm genes in two cohorts: the primary endpoint was rPFS in those with mutations in BRCA1/2 or ATM genes and then, if LYNPARZA showed clinical benefit, a formal analysis was performed of the overall trial population of patients with HRRm genes (BRCA1/2, ATM, CDK12 and 11 other HRRm genes; a key secondary endpoint).

    About LYNPARZA

    LYNPARZA® (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in HRR, such as mutations in BRCA and/or BRCA2. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.

    LYNPARZA is currently approved in a number of countries, including in the US, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with homologous recombination deficiency (HRD)-positive advanced ovarian cancer. LYNPARZA is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US and several other countries for the treatment of germline BRCA-mutated metastatic pancreatic cancer. LYNPARZA is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

    LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has been used to treat over 30,000 patients worldwide. LYNPARZA has the broadest and most advanced clinical trial development program of any PARP inhibitor, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. LYNPARZA is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

    About the AstraZeneca and Merck strategic oncology collaboration

    In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world's first PARP inhibitor, and selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and other compounds in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and other compounds in combination with their respective PD-L1 and PD-1 medicines.

    About AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    US-45202 Last Updated 09/20

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  2. ADAURA Phase III trial data at ESMO reinforce the proven clinical activity of TAGRISSO in treating central nervous system metastases

    Results from a prespecified exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca's TAGRISSO® (osimertinib) demonstrated a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC), after complete tumor resection.

    While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease.1-3 CNS recurrence…

    ADAURA Phase III trial data at ESMO reinforce the proven clinical activity of TAGRISSO in treating central nervous system metastases

    Results from a prespecified exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca's TAGRISSO® (osimertinib) demonstrated a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC), after complete tumor resection.

    While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease.1-3 CNS recurrence, when cancer spreads to the brain, is a frequent complication of EGFRm NSCLC and these patients have an especially poor prognosis.4,5

    Results were presented on September 19, 2020 during the Presidential Symposium of the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (abstract #LBA1) and simultaneously published with the primary results in The New England Journal of Medicine.

    This analysis showed that fewer patients treated with TAGRISSO in the adjuvant setting had recurrence events or deaths compared to placebo (11% versus 46%). Among patients whose cancer recurred, 38% of those treated with TAGRISSO had a metastatic recurrence compared to 61% of patients on placebo. TAGRISSO showed an 82% reduction in the risk of CNS recurrence or death (based on a hazard ratio [HR] of 0.18; 95% confidence interval [CI] 0.10-0.33; p<0.0001). Median CNS DFS was not yet reached in either arm.

    In a post-hoc analysis, the estimated probability of observing disease recurrence in the brain at 18 months for patients treated with TAGRISSO was less than 1% versus 9% for placebo among patients who had not experienced another type of recurrence. On the primary endpoint of DFS in patients with Stage II and IIIA disease, TAGRISSO in the adjuvant setting reduced the risk of disease recurrence or death by 83% (HR 0.17; 95% CI 0.12-0.23; p<0.0001).

    Masahiro Tsuboi, MD, PhD, director of the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East in Japan, and a principal investigator in the ADAURA Phase III trial, said: "It's time to change the notion that treatment for early-stage EGFR-mutated lung cancer ends after surgery, since recurrence rates are still very high even after adjuvant chemotherapy. These new data showing low rates of recurrence, particularly in the brain, combined with the remarkable disease-free survival benefit, clearly demonstrate that TAGRISSO provides patients with more time living cancer-free."

    José Baselga, Executive Vice President, Oncology R&D, said: "Once lung cancer has spread to the brain, outcomes are typically devastating for patients. We are now seeing TAGRISSO expanding on its proven efficacy in treating progression in the brain in the metastatic setting as a result of its ability to cross the blood-brain barrier. The striking new data show that TAGRISSO prevents the development of brain metastases in patients with early disease and reinforce that this medicine is truly transformative for patients with EGFR-mutated lung cancer. TAGRISSO should become the standard of care in the adjuvant setting, just as it is for patients with metastatic disease around the world."

    Summary of exploratory results on CNS recurrence in the ADAURA Phase III trial

     

    TAGRISSO

    n=339

    Placebo

    n=343

    CNS DFS

     

    HR (95% CI)

    0.18 (0.10-0.33);

    p-value

    p<0.0001

    CNS DFS events, patients (%):

    6 (2%)

    39 (11%)

    CNS recurrence

    4 (1%)

    33 (10%)

    Deathi

    2 (1%)

    6 (2%)

    DFS events, patients (%):

    37 (11%)

    159 (46%)

    Type of disease

    recurrence

    n=37

    n=157

    Local/regional only

    23 (62%)

    61 (39%)

    Distant

    14 (38%)

    96 (61%)

    Deathii

    0

    2 (1%)

    i. Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.

    ii. Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.

    The safety and tolerability of TAGRISSO in this trial was consistent with previous trials in the metastatic EGFRm NSCLC setting. Adverse events at Grade 3 or higher from all causes occurred in 10% of patients in the TAGRISSO arm versus 3% in the placebo arm as assessed by investigators.

    TAGRISSO is not currently approved in the adjuvant setting in any country. TAGRISSO received Breakthrough Therapy Designation in July 2020 for the adjuvant treatment of patients with early-stage EGFRm NSCLC after complete tumor resection with curative intent. TAGRISSO is approved for the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

    TAGRISSO IMPORTANT SAFETY INFORMATION

    • There are no contraindications for TAGRISSO
    • Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of the 1142 TAGRISSO-treated patients; 0.4% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
    • Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1142 TAGRISSO-treated patients in clinical trials, 0.9% were found to have a QTc >500 msec, and 3.6% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
    • Cardiomyopathy occurred in 2.6% of the 1142 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.9% of 908 patients who had baseline and at least one follow-up LVEF assessment. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
    • Keratitis was reported in 0.7% of 1142 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
    • Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
    • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
    • Most common adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue and decreased appetite

    INDICATIONS

    • TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

    Please see complete Prescribing Information, including Patient Information.

    About Lung cancer

    Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.6 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.7 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3

    For those with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.8 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.9,10

    Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.11-13 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signaling pathways that drive the growth of tumor cells.14

    About ADAURA

    ADAURA is a randomized, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with TAGRISSO 80 mg once-daily oral tablets or placebo for three years or until disease recurrence.

    The trial enrolled in more than 200 centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint is DFS in Stage II and IIIA patients and a key secondary endpoint is DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess OS.

    About TAGRISSO

    TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. TAGRISSO 40 mg and 80 mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm advanced NSCLC and EGFR T790M mutation-positive advanced NSCLC.

    AstraZeneca in lung cancer

    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease with the approved medicines gefitinib and TAGRISSO and its ongoing Phase III trials LAURA, NeoADAURA and FLAURA2.

    AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD, which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of four scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    References

    1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137:1191-1198.

    2. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:196-198.

    3. Datta D, et al. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. Chest. 2003;123:2096–2103.

    4. Rangachari D, et al. Brain Metastases in Patients with EGFR-Mutated or ALK-Rearranged Non-Small-Cell Lung Cancers. Lung Cancer. 2015;88:108–111.

    5. Ali A, et al. Survival of Patients with Non-small-cell Lung Cancer After a Diagnosis of Brain Metastases. Curr Oncol. 2013;20(4):e300-e306.

    6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed September 2020.

    7. LUNGevity Foundation. Types of Lung Cancer. Available at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer. Accessed September 2020.

    8. Pignon JP et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.

    9. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis. 2016;8:S494-S497.

    10. LUNGevity Foundation. Screening and Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection#1. Accessed September 2020.

    11. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-2812.

    12. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011;29:2121-2127.

    13. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89.

    14. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

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  3. PACIFIC Phase III trial data at ESMO also showed an estimated 35% of non-small cell lung cancer patients treated with IMFINZI® had not progressed after four years

    CASPIAN Phase III trial data also at ESMO underscored long-term benefit in a proportion of patients with extensive-stage small cell lung cancer

    Updated results from the PACIFIC Phase III trial showed AstraZeneca's IMFINZI® (durvalumab) demonstrated a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy (CRT).

    One in three patients with NSCLC are diagnosed at Stage III, where the majority of tumors…

    PACIFIC Phase III trial data at ESMO also showed an estimated 35% of non-small cell lung cancer patients treated with IMFINZI® had not progressed after four years

    CASPIAN Phase III trial data also at ESMO underscored long-term benefit in a proportion of patients with extensive-stage small cell lung cancer

    Updated results from the PACIFIC Phase III trial showed AstraZeneca's IMFINZI® (durvalumab) demonstrated a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy (CRT).

    One in three patients with NSCLC are diagnosed at Stage III, where the majority of tumors are unresectable (cannot be removed with surgery).1,2 Prior to the approval of IMFINZI in this setting, no new treatments beyond CRT had been available to these patients for decades.3,4,5

    The results from the updated post-hoc analyses showed an estimated four-year overall survival rate of 49.6% for IMFINZI versus 36.3% for placebo after CRT. Median OS was 47.5 months for IMFINZI versus 29.1 for placebo. With a maximum treatment course of one year, an estimated 35.3% of patients treated with IMFINZI had not progressed four years after enrollment versus 19.5% for placebo. These data build on The New England Journal of Medicine publication from 2018 demonstrating a significant benefit for IMFINZI in the OS primary endpoint.6

    Corinne Faivre-Finn, Professor at The University of Manchester and The Christie NHS Foundation Trust, and a lead investigator in the PACIFIC Phase III trial, said: "Previously, only 15 to 30 percent of patients with unresectable, Stage III non-small cell lung cancer survived five years, and the majority eventually progressed to metastatic disease. These data show about half of patients treated with IMFINZI survived four years, and an estimated 35 percent had not progressed, a remarkable advance in this curative-intent setting."

    José Baselga, Executive Vice President, Oncology R&D, said: "These unprecedented four-year results reinforce IMFINZI as the established standard of care in unresectable, Stage III non-small cell lung cancer and set a new survival benchmark in a setting where cure is the treatment goal. With data also at ESMO for CASPIAN in small cell lung cancer patients, IMFINZI continues to deliver impressive long-term benefits across different types of lung cancer."

    In the primary OS analysis of the PACIFIC Phase III trial, the most common adverse events (AE) (greater than or equal to 20%) among patients treated with IMFINZI versus placebo were cough (35.2% versus 25.2%), fatigue (24.0% versus 20.5%), dyspnea (22.3% versus 23.9%) and radiation pneumonitis (20.2% versus 15.8%). A grade 3 or 4 AE was experienced by 30.5% of patients treated with IMFINZI versus 26.1% for placebo, and 15.4% of patients discontinued treatment due to AEs with IMFINZI versus 9.8% for placebo.

    CASPIAN Phase III Trial Exploratory Subgroup Analyses in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) at the European Society for Medical Oncology (ESMO) Virtual Congress 2020

    New exploratory subgroup analyses from the CASPIAN Phase III trial of IMFINZI were conducted to characterize patients deriving long-term benefit. More than three times as many patients treated with IMFINZI plus chemotherapy were alive and progression free for one year or more (PFS ≥12 months) versus chemotherapy alone (17% versus 4.5%). Across all treatment arms, the subgroup of patients who were progression free at one year had a 75% chance of being alive at two years. In comparison, the subgroup of patients whose disease had progressed within one year (PFS <12 months) had a 10% chance of being alive at two years. Clinical characteristics did not appear to identify patients who derived long-term benefit.

    Patients with PFS ≥12 months received more cycles of IMFINZI treatment compared to patients with PFS <12 months (median of 25 cycles versus 7). Although patients with greater exposure to IMFINZI had numerically higher rates of immune-mediated AEs, the two subgroups had similar rates of severe AEs, serious AEs and AEs leading to discontinuation.

    The CASPIAN trial met the primary endpoint of OS in 2019, reducing the risk of death by 27% in patients with ES-SCLC treated with IMFINZI plus a choice of chemotherapy versus chemotherapy alone. The safety and tolerability of IMFINZI plus chemotherapy were consistent with the known safety profiles of these medicines. These results were published in The Lancet in 2019 and formed the basis of regulatory approvals around the world.7

    Results from the PACIFIC and CASPIAN Phase III trials were presented during the ESMO Virtual Congress on September 19 and September 21, 2020.

    Important Safety Information

    There are no contraindications for IMFINZI® (durvalumab).

    IMFINZI can cause serious, potentially fatal adverse reactions including immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, dermatologic reactions, other immune-mediated adverse reactions, infection, and infusion-related reactions. Please refer to the full Prescribing Information for important dosage modification and management information specific to adverse reactions.

    Immune-Mediated Pneumonitis

    IMFINZI can cause immune-mediated pneumonitis, defined as requiring use of corticosteroids. Fatal cases have been reported. Monitor patients for signs and symptoms of pneumonitis and evaluate with radiographic imaging when suspected. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently discontinue for Grade 3 or 4 pneumonitis.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, pneumonitis occurred in 5% of patients, including Grade 3 (0.8%), Grade 4 (<0.1%), and Grade 5 (0.3%) pneumonitis. Pneumonitis led to discontinuation of IMFINZI in 1.5% of the 1889 patients. The incidence of pneumonitis (including radiation pneumonitis) was higher in patients in the PACIFIC study who completed treatment with definitive chemoradiation within 42 days prior to initiation of IMFINZI (34%) compared to patients in other clinical studies (2.3%) in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI. In the PACIFIC study, the incidence of Grade 3 pneumonitis was 3.4% and of Grade 5 pneumonitis was 1.1% in the IMFINZI arm. In the PACIFIC study, pneumonitis led to discontinuation of IMFINZI in 6% of patients.

    The frequency and severity of immune-mediated pneumonitis were similar whether IMFINZI was given as a single agent in patients with various cancers or in combination with chemotherapy in patients with ES-SCLC.

    Immune-Mediated Hepatitis

    IMFINZI can cause immune-mediated hepatitis, defined as requiring use of corticosteroids. Fatal cases have been reported. Monitor patients for signs and symptoms of hepatitis during and after discontinuation of IMFINZI, including clinical chemistry monitoring. Administer corticosteroids for Grade 2 or higher elevations of ALT, AST, and/or total bilirubin. Withhold IMFINZI for ALT or AST greater than 3 but less than or equal to 8 times the ULN or total bilirubin greater than 1.5 but less than or equal to 5 times the ULN; permanently discontinue IMFINZI for ALT or AST greater than 8 times the ULN or total bilirubin greater than 5 times the ULN or concurrent ALT or AST greater than 3 times the ULN and total bilirubin greater than 2 times the ULN with no other cause.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, hepatitis occurred in 12% of patients, including Grade 3 (4.4%), Grade 4 (0.4%), and Grade 5 (0.2%) hepatitis. Hepatitis led to discontinuation of IMFINZI in 0.7% of the 1889 patients.

    Immune-Mediated Colitis

    IMFINZI can cause immune-mediated colitis, defined as requiring use of corticosteroids. Administer corticosteroids for Grade 2 or greater colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea; permanently discontinue for Grade 3 or 4 colitis or diarrhea.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, colitis or diarrhea occurred in 18% of patients, including Grade 3 (1.0%) and Grade 4 (0.1%) immune-mediated colitis. Diarrhea or colitis led to discontinuation of IMFINZI in 0.4% of the 1889 patients.

    Immune-Mediated Endocrinopathies

    IMFINZI can cause immune-mediated endocrinopathies, including thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus, and hypophysitis/hypopituitarism. Monitor patients for clinical signs and symptoms of endocrinopathies.

    • Thyroid disorders—Monitor thyroid function prior to and periodically during treatment. Initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated. Withhold IMFINZI for Grades 2–4 hyperthyroidism, until clinically stable. Continue IMFINZI for hypothyroidism.

      In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, hypothyroidism occurred in 11% of patients, while hyperthyroidism occurred in 7% of patients. Thyroiditis occurred in 0.9% of patients, including Grade 3 (<0.1%) thyroiditis. Hypothyroidism was preceded by thyroiditis or hyperthyroidism in 25% of patients.
    • Adrenal insufficiency—Administer corticosteroids as clinically indicated and withhold IMFINZI until clinically stable for Grade 2 or higher adrenal insufficiency. In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, adrenal insufficiency occurred in 0.7% of patients, including Grade 3 (<0.1%) adrenal insufficiency.
    • Type 1 diabetes mellitus—Initiate treatment with insulin as clinically indicated. Withhold IMFINZI for Grades 2–4 type 1 diabetes mellitus, until clinically stable. In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, type 1 diabetes mellitus occurred in <0.1% of patients.
    • Hypophysitis—Administer corticosteroids and hormone replacement as clinically indicated and withhold IMFINZI until clinically stable for Grade 2 or higher hypophysitis. Hypopituitarism leading to adrenal insufficiency and diabetes insipidus occurred in <0.1% of 1889 patients with various cancers who received IMFINZI.

    Immune-Mediated Nephritis

    IMFINZI can cause immune-mediated nephritis, defined as evidence of renal dysfunction requiring use of corticosteroids. Fatal cases have occurred. Monitor patients for abnormal renal function tests prior to and periodically during treatment with IMFINZI. Administer corticosteroids as clinically indicated. Withhold IMFINZI for creatinine greater than 1.5 to 3 times the ULN; permanently discontinue IMFINZI and administer corticosteroids in patients with creatinine greater than 3 times the ULN.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, nephritis (reported as any of the following: increased creatinine or urea, acute kidney injury, renal failure, decreased glomerular filtration rate, tubulointerstitial nephritis, decreased creatinine clearance, glomerulonephritis, and nephritis) occurred in 6.3% of the patients including Grade 3 (1.1%), Grade 4 (0.2%), and Grade 5 (0.1%) nephritis. IMFINZI was discontinued in 0.3% of the 1889 patients.

    Immune-Mediated Dermatologic Reactions

    IMFINZI can cause immune-mediated rash. Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) has occurred with other products in this class. Administer corticosteroids for Grade 2 rash or dermatitis lasting for more than 1 week or for Grade 3 or 4 rash or dermatitis. Withhold IMFINZI for Grade 2 rash or dermatitis lasting longer than 1 week or Grade 3 rash or dermatitis; permanently discontinue IMFINZI in patients with Grade 4 rash or dermatitis.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, 26% of patients developed rash or dermatitis and 0.4% of the patients developed vitiligo. Rash or dermatitis led to discontinuation of IMFINZI in 0.1% of the 1889 patients.

    Other Immune-Mediated Adverse Reactions

    IMFINZI can cause severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system. While immune-mediated reactions usually manifest during treatment with IMFINZI, immune-mediated adverse reactions can also manifest after discontinuation of IMFINZI. For suspected immune-mediated adverse reactions, exclude other causes and initiate corticosteroids as clinically indicated. Withhold IMFINZI for Grade 3 immune-mediated adverse reactions, unless clinical judgment indicates discontinuation; permanently discontinue IMFINZI for Grade 4 adverse reactions.

    The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1889 patients who received IMFINZI: aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis, and ocular inflammatory toxicity, including uveitis and keratitis. In patients who received IMFINZI in clinical studies outside of the pooled dataset, myasthenia gravis occurred at an incidence of less than 0.1%. Permanently discontinue IMFINZI if myasthenia gravis does not resolve to ≤ Grade 1 within 30 days or if there are signs of respiratory and/or autonomic insufficiency. Additional clinically significant immune-mediated adverse reactions have been seen with other products in this class (see Warnings and Precautions Section 5.7 of IMFINZI full Prescribing Information).

    Infection

    IMFINZI can cause serious infections, including fatal cases. Monitor patients for signs and symptoms of infection and treat as clinically indicated. Withhold IMFINZI for Grade 3 or 4 infection, until clinically stable.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, infections occurred in 43% of patients, including Grade 3 (8%), Grade 4 (1.9%), and Grade 5 (1.0%). The overall incidence of infections in IMFINZI-treated patients in the PACIFIC study (56%) was higher compared to patients in other clinical studies (38%) in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI. In patients with UC in Study 1108 (n=182), the most common Grade 3 or higher infection was urinary tract infections, which occurred in 4% of patients. In patients with Stage III NSCLC in the PACIFIC study, the most common Grade 3 or higher infection was pneumonia, which occurred in 5% of patients.

    Infusion-Related Reactions

    IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor patients for signs and symptoms of an infusion-related reaction. Interrupt or slow the rate of infusion for Grades 1–2 infusion-related reactions; permanently discontinue for Grades 3–4 infusion-related reactions.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, infusion-related reactions occurred in 2.2% of patients, including Grade 3 (0.3%).

    Embryo-Fetal Toxicity

    Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. There are no data on the use of IMFINZI in pregnant women. Advise pregnant women of the potential risk to a fetus and advise women of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of IMFINZI.

    Lactation

    There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for at least 3 months after the last dose.

    Most Common Adverse Reactions

    • In patients with UC in Study 1108 (n=182), the most common adverse reactions (≥15%) were fatigue (39%), musculoskeletal pain (24%), constipation (21%), decreased appetite (19%), nausea (16%), peripheral edema (15%), and urinary tract infection (15%). The most common Grade 3 or 4 adverse reactions (≥3%) were fatigue, urinary tract infection, musculoskeletal pain, abdominal pain, dehydration, and general physical health deterioration
    • In patients with UC in Study 1108, discontinuation due to adverse reactions occurred in 3.3% of patients. Serious adverse reactions occurred in 46% of patients. The most frequent serious adverse reactions (>2%) were acute kidney injury (4.9%), urinary tract infection (4.4%), musculoskeletal pain (4.4%), liver injury (3.3%), general physical health deterioration (3.3%), sepsis, abdominal pain, and pyrexia/tumor associated fever (2.7% each)
    • In patients with Stage III NSCLC in the PACIFIC study (IMFINZI n=475), the most common adverse reactions (≥20% of patients) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis/radiation pneumonitis (3.4%) and pneumonia (7%)
    • In patients with Stage III NSCLC in the PACIFIC study (IMFINZI n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2% of patients) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms
    • In patients with extensive-stage SCLC in the CASPIAN study (n=265), the most common adverse reactions (≥20%) were nausea, fatigue/asthenia, and alopecia. The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%)
    • In patients with extensive-stage SCLC in the CASPIAN study (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy

    The safety and effectiveness of IMFINZI have not been established in pediatric patients.

    Indications

    IMFINZI is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who:

    • Have disease progression during or following platinum-containing chemotherapy.
    • Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

    This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

    IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

    IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

    Please see complete Prescribing Information, including Medication Guide.

    NOTES TO EDITORS

    About Lung cancer

    Lung cancer is the leading cause of cancer death among both men and women and accounts for about one fifth of all cancer deaths.8 Lung cancer is broadly split into NSCLC and SCLC, with about 85% classified as NSCLC and 15% classified as SCLC.9

    Stage III NSCLC (locally advanced) is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery.10 Stage III disease is different from Stage IV disease, when the cancer has spread (metastasized), as the majority of Stage III patients are treated with curative intent.10,11 In 2015, Stage III NSCLC was estimated to affect nearly 200,000 patients in the following eight key countries: China, France, Germany, Italy, Japan, Spain, UK, and the US, with approximately 43,000 cases in the US alone.2

    SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly, despite initial response to chemotherapy.12,13 About two thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.14 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.14

    About PACIFIC

    The PACIFIC trial was a Phase III, randomized, double-blinded, placebo-controlled, multi-center trial of IMFINZI (durvalumab) as treatment in "all-comer'" patients (regardless of PD-L1 status) with unresectable, Stage III NSCLC whose disease had not progressed following concurrent platinum-based CRT.

    The trial was conducted at 235 centers across 26 countries involving 713 patients. The primary endpoints of the trial were PFS and OS, and secondary endpoints included landmark PFS and OS, objective response rate (ORR) and duration of response (DoR).

    About CASPIAN

    CASPIAN is a randomized, open-label, multi-center, global, Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared IMFINZI in combination with etoposide and either carboplatin or cisplatin chemotherapy, or IMFINZI and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with up to four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial is being conducted in more than 200 centers across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint is OS in each of the experimental arms.

    About IMFINZI® (durvalumab)

    IMFINZI is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses.

    IMFINZI is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. IMFINZI is approved for the 1st-line treatment of ES-SCLC in combination with standard of care (SoC) chemotherapy in the US and Singapore. IMFINZI is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

    As part of a broad development program, IMFINZI is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumors.

    About AstraZeneca Support Programs

    AstraZeneca strives to ensure that appropriate patients and their oncologists have access to IMFINZI and relevant support resources. These include educational resources, an Oncology Nurse Educator program and affordability and reimbursement programs, such as Access 360™.

    Additionally, AstraZeneca has launched Lighthouse, a program that provides support to patients during any immune-mediated adverse events they may encounter during treatment, through medically trained Lighthouse Advocates. The program aims to make patients' treatment experience as comfortable as possible. Find out more about Lighthouse at LighthouseProgram.com or call 1-855-LHOUSE1(1-855-546-8731).

    About AstraZeneca in lung cancer

    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    An extensive Immuno-Oncology development program focuses on lung cancer patients without a targetable genetic mutation which represent up to three-quarters of all patients with lung cancer.15 IMFINZI, an anti-PDL1 antibody, is in development for patients with advanced disease (POSEIDON and PEARL Phase III trials) and for patients in earlier stages of disease including potentially curative settings (MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC Phase III trials) both as monotherapy and in combination with tremelimumab and/or chemotherapy.

    About AstraZeneca's approach to Immuno-Oncology (IO)

    Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body's immune system to attack tumors. Our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumor immune suppression. We are invested in using IO approaches that deliver long-term survival for new groups of patients across tumor types.

    We are pursuing a comprehensive clinical-trial program that includes IMFINZI as a monotherapy and in combination with tremelimumab in multiple tumor types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca's Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumors.

    About AstraZeneca in Oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advancing oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca's main capabilities, we are actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in hematology.

    By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    1. Antonia SJ, et al. PACIFIC Investigators. Durvalumab After Chemoradiotherapy In Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919-1929.

    2. Kantar Health CancerMPact. Treatment Modality. http://cancermpact.khapps.com. Accessed September 2020.

    3. Curran WJ, et al. Sequential vs Concurrent Chemoradiation for Stage III Non–Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452–1460.

    4. NCCN Clinical Practice Guidelines in Oncology. Non-small cell lung cancer, version 8. 2017 Aug 3.

    5. Hanna N, et al. Current Standards and Clinical Trials in Systemic Therapy for Stage III Lung Cancer: What is New? Am Soc Clin Oncol Educ Book. 2015;e442-447.

    6. Antonia SJ, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.

    7. Paz-Ares, et al. Durvalumab Plus Platinum-Etoposide Versus Platinum-Etoposide in First-Line Treatment of Extensive-Stage Small Cell Lung Cancer (CASPIAN): A Randomized, Controlled, Open-Label, Phase 3 Trial. The Lancet. 2019;394(10,212):1929-1939.

    8. American Cancer Society. Key Statistics for Lung Cancer. Available at https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed September 2020.

    9. American Cancer Society. What is Lung Cancer? Available at https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed September 2020.

    10. ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Available at: https://www.cancer.net/cancer-types/lung-cancer/view-all. Accessed September 2020.

    11. Cheema PK, et al. Perspectives on Treatment Advances For Stage III Locally Advanced Unresectable Non-Small-Cell Lung Cancer. Curr Oncol. 2019;26(1):37-42.

    12. Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? J Oncol Pract. 2018;14(6):369-370.

    13. National Cancer Institute. NCI Dictionary – Small Cell Lung Cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed September 2020.

    14. Cancer.Net. Lung Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/33776/view-all. Accessed September 2020.

    15. Pakkala, S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3(15):e120858.

    US-43737 Last Updated 9/20

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  4. Five-year data from the SOLO-1 Phase III trial is the longest follow-up analysis for any PARP inhibitor in the 1st-line maintenance setting

    AstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the US and Canada) today announced that LYNPARZA demonstrated a long-term progression-free survival (PFS) benefit versus placebo as a 1st-line maintenance treatment in patients with newly diagnosed, advanced BRCA-mutated (BRCAm) ovarian cancer who had a complete or partial response following platinum-based chemotherapy.

    Ovarian cancer ranks fifth in cancer deaths among women in the U.S., and in 2020, an estimated 21,750 women in the U.S. will receive a new diagnosis and about 13,940 women will die from ovarian cancer.1

    Five-year follow-up…

    Five-year data from the SOLO-1 Phase III trial is the longest follow-up analysis for any PARP inhibitor in the 1st-line maintenance setting

    AstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the US and Canada) today announced that LYNPARZA demonstrated a long-term progression-free survival (PFS) benefit versus placebo as a 1st-line maintenance treatment in patients with newly diagnosed, advanced BRCA-mutated (BRCAm) ovarian cancer who had a complete or partial response following platinum-based chemotherapy.

    Ovarian cancer ranks fifth in cancer deaths among women in the U.S., and in 2020, an estimated 21,750 women in the U.S. will receive a new diagnosis and about 13,940 women will die from ovarian cancer.1

    Five-year follow-up data from the Phase III SOLO-1 trial showed LYNPARZA reduced the risk of disease progression or death by 67% (based on a hazard ratio [HR] of 0.33; 95% confidence interval [CI] 0.25-0.43) and improved PFS to a median of 56.0 months versus 13.8 months for placebo. At five years, 48.3% of patients treated with LYNPARZA remained free from disease progression versus 20.5% on placebo. The median duration of treatment with LYNPARZA was 24.6 months versus 13.9 months with placebo.

    Susana Banerjee, one of the investigators from the SOLO-1 trial and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Reader at the Institute of Cancer Research, London, said: "For patients with newly diagnosed BRCA-mutated advanced ovarian cancer, the benefit derived from two years of maintenance treatment with LYNPARZA continued long after treatment ended. After five years, almost half of these women were free of cancer progression. These results represent a significant step forward in the treatment of BRCA-mutated ovarian cancer."

    José Baselga, Executive Vice President, Oncology R&D, said: "Once a patient's ovarian cancer recurs, it has historically been incurable. Even at an advanced stage, we have shown that maintenance treatment with LYNPARZA can help patients achieve sustained remission. Today's results further underline the critical importance of identifying a patient's biomarker status at the time of diagnosis to be able to offer a treatment that may help delay disease progression."

    Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck, said: "This is the first trial of a PARP inhibitor to read out a five year follow up and showed LYNPARZA improved progression-free survival to over four and a half years versus 13.8 months with placebo following response to 1st-line platinum-based chemotherapy. This latest data represents a major and significant milestone in a disease which has historically had such a poor prognosis."

    Summary of results

     

    Progression-free survival

    Recurrence-free survival*

    LYNPARZA

    N=260

    Placebo

    N=131

    LYNPARZA

    N=189

    Placebo

    N=101

    Events, n (%)

    118 (45)

    100 (76)

    79 (42)

    74 (73)

    Median, m

    56.0

    13.8

    NR

    15.3

    HR (95%CI)

    0.33 (0.25–0.43)

     

    0.37 (0.27–0.52)

    Patients progression or recurrence free at timepoint, % (Kaplan-Meier estimates)

    1y

    87.7

    51.4

    91.0

    58.0

    2y

    73.6

    34.6

    77.2

    39.0

    3y

    60.1

    26.9

    64.0

    28.9

    4y

    52.3

    21.5

    55.2

    23.0

    5y

    48.3

    20.5

    51.9

    21.8

    *Defined post hoc as time from randomization to disease recurrence* or death for patients in complete response to platinum-based chemotherapy at baseline; patients had CR at baseline based on electronic case report form data. CI, confidence interval; HR, hazard ratio; NR, not reached

    The safety profile of LYNPARZA was consistent with previous observations. The most common adverse events (AEs) ≥20% were nausea (77%), fatigue/asthenia (63%), vomiting (40%), anemia (39%) and diarrhea (34%). The most common ≥ grade 3 AEs were anemia (22%) and neutropenia (9%). Twelve percent of patients on LYNPARZA discontinued treatment due to an AE.

    The results were presented on Friday, September 18, during the 2020 European Society of Medical Oncology (ESMO) virtual congress.

    The Phase III SOLO-1 trial met the primary endpoint of PFS in June 2018, which formed the basis of approvals in the US, the EU, Japan, China, and several other countries.2

    IMPORTANT SAFETY INFORMATION

    CONTRAINDICATIONS

    There are no contraindications for LYNPARZA.

    WARNINGS AND PRECAUTIONS

    Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

    Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

    If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

    Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

    Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

    Females

    Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

    Males

    Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

    Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

    ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

    ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

    Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

    In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

    ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

    Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

    ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

    ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

    ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

    ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

    DRUG INTERACTIONS

    Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

    CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

    CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

    USE IN SPECIFIC POPULATIONS

    Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

    Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

    Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

    Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

    INDICATIONS

    LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

    First-Line Maintenance BRCAm Advanced Ovarian Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

    In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

    • a deleterious or suspected deleterious BRCA mutation, and/or
    • genomic instability

    Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Maintenance Recurrent Ovarian Cancer

    For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

    Advanced gBRCAm Ovarian Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    gBRCAm, HER2-Negative Metastatic Breast Cancer

    For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

    About Ovarian Cancer

    Approximately 21,750 women in the United States will be diagnosed with ovarian cancer (including ovarian, fallopian tube and primary peritoneal cancers) in 2020. Among women in the United States, it is the fifth leading cause of cancer death.1

    The risk of developing ovarian cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations.3

    About SOLO-1

    SOLO-1 was a Phase III randomized, double-blinded, placebo-controlled, multi-center trial to evaluate the efficacy and safety of LYNPARZA tablets (300 mg twice daily) as a maintenance monotherapy compared with placebo in patients with newly diagnosed BRCAm advanced ovarian cancer following first-line platinum-based chemotherapy. The trial randomized 391 patients with a deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy.

    Patients were randomized (2:1) to receive LYNPARZA or placebo for up to two years or until disease progression. Patients who had a partial response at two years were permitted to stay on therapy at the investigator's discretion.4 The primary endpoint was PFS and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.2

    About LYNPARZA

    LYNPARZA® (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair, such as mutations in BRCA1 and/or BRCA2.4,5,6 Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.7 LYNPARZA is being tested in a range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.

    LYNPARZA is currently approved in a number of countries, including those in the US, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with homologous recombination deficiency (HRD)-positive advanced ovarian cancer. LYNPARZA is approved in the US, Japan, and a number of other countries for the treatment of germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US and several other countries for the treatment of germline BRCA-mutated metastatic pancreatic cancer. LYNPARZA is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

    LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has been used to treat over 30,000 patients worldwide. LYNPARZA has the broadest and most advanced clinical trial development program of any PARP inhibitor, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. LYNPARZA is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

    About the AstraZeneca and Merck Strategic Oncology Collaboration

    In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world's first PARP inhibitor, and KOSELUGO (selumetinib), a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and other compounds in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and KOSELUGO in combination with their respective PD-L1 and PD-1 medicines.

    About AstraZeneca in Oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

    REFERENCES

    1. American Cancer Society. About Ovarian Cancer. Available Online. Accessed September 2020.
    2. US National Institutes of Health. Olaparib Maintenance Monotherapy in Patients with BRCA Mutated Ovarian Cancer Following First-Line Platinum Based Chemotherapy. Available Online. Accessed October 2020.
    3. National Cancer Institute. BRCA1 and BRCA2: cancer risk and genetic testing. Available Online. Accessed September 2020.
    4. LYNPARZA® (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
    5. O'Connor M. Targeting the DNA damage response in cancer. Mol Cell. 2015; Accessed September 2020.
    6. Tutt AN, Lord CJ, McCabe N. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb Symp Quant Biol. 2005;70:139-148.
    7. Brown JS et al. Targeting DNA Repair in Cancer: Beyond PARP Inhibitors. Cancer Discov. 2017;(1):20-37.

    US-45203 Last Updated 9/20

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  5. Leading biopharmaceutical company to unify quality management and content to increase operational efficiency and agility

    Veeva Systems (NYSE:VEEV) today announced that AstraZeneca has selected Veeva Vault QMS and Veeva Vault QualityDocs to unify quality management and content on a single cloud platform. Veeva Vault Quality Suite enables AstraZeneca to streamline quality processes across the enterprise, increasing real-time visibility, efficiency, and speed.

    "As AstraZeneca builds on a strong foundation for world-class quality systems and processes," said Anthony Morandi, vice president of quality at AstraZeneca. "Veeva Vault Quality Suite will provide us with a standardized, scalable, efficient, and compliant approach to managing our global…

    Leading biopharmaceutical company to unify quality management and content to increase operational efficiency and agility

    Veeva Systems (NYSE:VEEV) today announced that AstraZeneca has selected Veeva Vault QMS and Veeva Vault QualityDocs to unify quality management and content on a single cloud platform. Veeva Vault Quality Suite enables AstraZeneca to streamline quality processes across the enterprise, increasing real-time visibility, efficiency, and speed.

    "As AstraZeneca builds on a strong foundation for world-class quality systems and processes," said Anthony Morandi, vice president of quality at AstraZeneca. "Veeva Vault Quality Suite will provide us with a standardized, scalable, efficient, and compliant approach to managing our global quality systems and continued growth."

    Driving manufacturing agility through automation is foundational to AstraZeneca's strategic digital transformation initiative. With the Vault Quality Suite, AstraZeneca can easily collaborate with external suppliers and partners to increase transparency and bring drugs to patients faster.

    "We are pleased to partner with AstraZeneca to help enable end-to-end quality management," said Mike Jovanis, vice president of Vault Quality at Veeva. "We are looking forward to continuing to help AstraZeneca streamline quality processes and drive greater agility."

    Learn how life sciences companies are modernizing quality management with the Vault Quality Suite at the upcoming Veeva R&D and Quality Summit, October 13-14, 2020. The online event is open to life sciences industry professionals. Register and view the agenda at veeva.com/Summit.

    Additional Information

    For more on Veeva Vault Quality Suite, visit: veeva.com/Quality

    Connect with Veeva on LinkedIn: linkedin.com/company/veeva-systems

    Follow @veevasystems on Twitter: twitter.com/veevasystems

    Like Veeva on Facebook: facebook.com/veevasystems

    About AstraZeneca

    AstraZeneca (NYSE:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

    About Veeva Systems

    Veeva Systems Inc. is a leader in cloud solutions—including data, software, and services—for the global life sciences industry. Committed to innovation, product excellence, and customer success, Veeva serves more than 900 customers, ranging from the world's largest pharmaceutical companies to emerging biotechs. The company is headquartered in the San Francisco Bay Area, with offices throughout North America, Europe, Asia, and Latin America. For more information, visit veeva.com.

    Forward-looking Statements

    This release contains forward-looking statements, including the market demand for and acceptance of Veeva's products and services, the results from use of Veeva's products and services, and general business conditions (including the on-going impact of COVID-19), particularly within the life sciences industry. Any forward-looking statements contained in this press release are based upon Veeva's historical performance and its current plans, estimates, and expectations, and are not a representation that such plans, estimates, or expectations will be achieved. These forward-looking statements represent Veeva's expectations as of the date of this press announcement. Subsequent events may cause these expectations to change, and Veeva disclaims any obligation to update the forward-looking statements in the future. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially. Additional risks and uncertainties that could affect Veeva's financial results are included under the captions, "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations," in the company's filing on Form 10-Q for the period ended July 31, 2020. This is available on the company's website at veeva.com under the Investors section and on the SEC's website at . Further information on potential risks that could affect actual results will be included in other filings Veeva makes with the SEC from time to time.

    ® 2020 Veeva Systems Inc. All rights reserved. Veeva and the Veeva logo are trademarks of Veeva Systems Inc.

    Veeva Systems Inc. owns other registered and unregistered trademarks.

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