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LYNPARZA® (olaparib) Approved by US FDA in Germline BRCA-Mutated Metastatic Breast CancerAstraZeneca and Merck (Merck: known as MSD outside the US and Canada) today announced that the US Food and Drug Administration (FDA) has approved LYNPARZA® (olaparib), for use in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor positive (HR+) breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Patients are selected for therapy based on an FDA-approved companion diagnostic from Myriad Genetics.1 Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit, AstraZeneca, said: "This new approval for LYNPARZA makes it the first and only PARP inhibitor approved in metastatic breast cancer, and the only PARP inhibitor approved beyond ovarian cancer. This is significant for breast cancer patients, as the identification of BRCA status, in addition to hormone receptor and HER2 status, becomes a potentially critical step in the management of their disease." Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said: "This additional approval for LYNPARZA represents an important advance for women with HER2-negative metastatic breast cancer with a germline BRCA mutation, which is a difficult-to-treat cancer. Moreover, this approval adds further impetus to our important collaboration with AstraZeneca in developing cancer therapies." The approval was based on data from the randomized, open-label, Phase III OlympiAD trial, which investigated LYNPARZA versus physician's choice of chemotherapy (capecitabine, eribulin or vinorelbine). In the trial, LYNPARZA significantly prolonged progression-free survival (PFS) compared with chemotherapy, and reduced the risk of disease progression or death by 42% (HR 0.58; 95% CI 0.43-0.80; P=0.0009 median 7.0 vs 4.2 months). Patients with measurable disease taking LYNPARZA (n=167) experienced an objective response rate of 52% (95% CI 44-60), double the response rate for those in the chemotherapy arm (n=66) which was 23% (95% CI 13-35). Additionally, patients experienced a confirmed complete response rate of 7.8% for LYNPARZA compared to 1.5% for the chemotherapy arm. The data from the OlympiAD trial can be found in the June 2017 issue of the New England Journal of Medicine.1,2 Dr. Susan M. Domchek, Executive Director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania, and a national leader on the OlympiAD trials said: "Patients diagnosed with BRCA-related metastatic breast cancer are often younger than other breast cancer patients, and their disease is often much more aggressive and difficult to treat. While there is currently no cure for metastatic breast cancer, today's approval offers a new, targeted option that may help to delay disease progression for these patients." Sue Friedman, Executive Director and founder of the nonprofit organization, Facing Our Risk of Cancer Empowered (FORCE), said: "We know there are limited treatment options for patients with metastatic breast cancer. For the portion of the 155,000 women in the US living with metastatic breast cancer who have an inherited BRCA mutation, today's news is encouraging. By undergoing genetic testing for BRCA mutations, we can gain critical information that will inform personalized treatment options specifically for women with this mutation." The most common adverse reactions (=20%) in the OlympiAD trial of patients who received LYNPARZA were nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%) and headache (20%). The percentage of patients who discontinued treatment in the LYNPARZA arm was 5% compared to the chemotherapy arm which was 8%. Please see Important Safety Information below. This is the third indication approved for LYNPARZA in the US, where it has been used to treat nearly 4,000 advanced ovarian cancer patients.1,3 LYNPARZA has a broad clinical development program, and AstraZeneca and Merck are working together to deliver LYNPARZA as quickly as possible to more patients across multiple settings, including breast, ovarian, prostate and pancreatic cancers.4-7 Sustainable and Ongoing Externalization Revenue Under the oncology collaboration with Merck, announced in July 2017, AstraZeneca is potentially eligible for more than $6 billion of future Sustainable and Ongoing Externalization Revenue in the form of sales-related and approval-related payments in addition to option payments until 2019. Following this new approval for LYNPARZA, AstraZeneca will receive $70 million in Sustainable and Ongoing Externalization Revenue. IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS 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
Males
ADVERSE REACTIONS-Maintenance Setting 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 laboratory abnormalities (Grades 1-4) in =25% of patients in clinical trials of LYNPRZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), increase in mean corpuscular volume (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 breast cancer 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%).
DRUG INTERACTIONS
USE IN SPECIFIC POPULATIONS
DOSING AND ADMINISTRATION
INDICATIONS 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. 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. In patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously 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 treatment. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Please see complete Prescribing Information, including Patient Information (Medication Guide). - ENDS - NOTES TO EDITORS
About OlympiAD Patients in the OlympiAD trial had HER2-negative gBRCA1- or gBRCA2-mutated breast cancer, which was HR+ or triple negative, and received LYNPARZA for metastatic disease. Approximately half of the patients in the LYNPARZA and chemotherapy arm of the trial were HR+ (n=152), and approximately half were triple negative (n=150). Among the 205 patients treated with LYNPARZA, the median age was 44 years (range: 22 to 76). Before enrollment, patients had prior treatment with an anthracycline (unless contraindicated) and a taxane chemotherapy either in the neoadjuvant, adjuvant or metastatic setting and no more than two prior lines of chemotherapy for metastatic disease. HR+ patients had received at least one endocrine medicine or were not eligible for endocrine medicines. Prior treatments with endocrine medicines were not counted as prior lines of chemotherapy.2,8 The primary endpoint of the trial was PFS as measured by a Blinded Independent Central Review.2,8 Secondary endpoints included overall survival, time to second progression or death, objective response rate, and effect on health-related quality of life.2,8
About Metastatic Breast Cancer (MBC) MBC is the most advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumor site to other parts of the body outside of the breast.11,12 Despite the increase in treatment options during the past three decades, there is currently no cure for patients diagnosed with MBC and only 26.9% of patients survive five years after diagnosis.13-15 Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving, or at least maintaining, a patient's quality of life.16 It is estimated that in 2018, there will be approximately 155,000 women in the US living with MBC, and this number is projected to increase to approximately 160,000 by the year 2020.17
About Germline BRCA Mutations
About LYNPARZA® (olaparib) LYNPARZA is being investigated in a range of DDR-deficient tumor types and is the foundation of AstraZeneca's industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.19-21
About the AstraZeneca and Merck Strategic Oncology Collaboration
About AstraZeneca in Oncology 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 For more information, please visit www.astrazeneca-us.com and follow us on Twitter (News - Alert) @AstraZenecaUS. Media Inquiries
Michele Meixell +1 302 885 2677 References
US-14448 Last Updated 1/18 View source version on businesswire.com: http://www.businesswire.com/news/home/20180112005500/en/ |