Lynparza® (olaparib) Receives New Indication for BRCA-Mutated Metastatic Breast Cancer

Lynparza has been shown to reduce the risk of disease progression or death by 42 per cent compared to standard of care chemotherapy.ⁱ

MISSISSAUGA, May 10, 2018 /CNW/ - AstraZeneca today announced that Health Canada has approved Lynparza^® (olaparib) tablets, as a monotherapy for the treatment of adult 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 progressed on or be considered inappropriate for endocrine therapy. Germline BRCA mutation must be confirmed before Lynparza treatment is initiated.ⁱⁱ

"The approval of Lynparza for BRCA-mutated metastatic breast cancer represents a significant step for patients with this form of advanced breast cancer as it is the first drug to be available for these specific tumours," said Dr. Karen Gelmon, Professor of Medicine at the University of British Columbia. "By using PARP inhibitors, the treatment is able to target the BRCA-mutated tumour cells and repair the damaged DNA with fewer side effects than currently used chemotherapies, which may be more toxic for patients."

Health Canada's approval of Lynparza for gBRCAm HER2-negative metastatic breast cancer was based on data from the phase III, randomized, open-label, multicentre, active-controlled trial, OlympiAD (Study D0819C00003).ⁱⁱⁱ

The OlympiAD study met its primary objective of demonstrating a statistically significant and clinically meaningful improvement in progression-free survival for Lynparza compared with the chemotherapy comparator arm, reducing the risk of disease progression or death by 42 per cent (HR 0.58; 95% CI 0.43-0.80; p=0.0009; median 7.0 months [95% CI 5.7-8.3] for Lynparza vs. 4.2 months [95% CI 2.8-4.3] for comparator).^iv

"Women with metastatic breast cancer want to live the best life they can, for as long as they can. While each has her own reason – to reach a milestone, or to create more memories with her family – enabling more quality time is closely linked to having a toolbox of treatments that control the disease and let them continue to live on," said MJ DeCoteau, founder and executive director of Rethink Breast Cancer. "The approval of Lynparza offers a new, effective option to patients with BRCA-mutated metastatic breast cancer that will help them live a better life longer." 

This is the third approved indication for Lynparza in Canada, first granted marketing authorization with conditions in April 2016, in capsules as monotherapy for the maintenance treatment for patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.^v

On May 4, 2018, Health Canada approved Lynparza tablets, as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed, high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy. Marketing authorization with conditions was granted for treatment of patients with BRCA wild-type status, pending the results of trials to verify its clinical benefit. The indication also coincides with the approval of a new tablet formulation of Lynparza, which reduces daily pill intake from 16 capsules to four tablets daily.

The most common adverse reactions (≥20%) in the OlympiAD trial for patients who received Lynparza were nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (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%.

About BRCA in Breast Cancer
Breast cancer is the most common cancer among Canadian women.^vi It is estimated that 26,300 women and 230 men in Canada were diagnosed with breast cancer in 2017.^vii

The risk of developing breast cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations.^viii Women who carry a mutation in their BRCA1 or BRCA2 genes have a 40-85 per cent chance of developing breast cancer in their lifetime, are more likely to develop breast cancer at a younger age (before menopause), and often have multiple family members with the disease.^ix This genetic marker indicates an increased risk, but also now offers the possibility of a targeted treatment option for women already diagnosed with germline BRCA-mutated breast cancer.^x

About Lynparza (olaparib)
Lynparza was the first Health Canada-approved oral poly (ADP-ribose) polymerase (PARP) inhibitor that may exploit tumor DNA damage response (DDR) pathway deficiencies to potentially kill cancer cells. ^xi It is the first PARP inhibitor to be approved for treatment of patients with advanced ovarian cancer and BRCA-mutated, HER2-negative metastatic breast cancer.

Health Canada first issued a Notice of Compliance with Conditions for Lynparza capsules in April 2016, which followed the announcement of the approval of Lynparza by the FDA and the European Union in December 2014. In May 2018, Health Canada granted approval for the new tablet formulation of Lynparza for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy. For treatment of patients with BRCA wild type status, marketing authorization with conditions was granted, pending the results of trials to verify its clinical benefit.

AstraZeneca is conducting multiple Lynparza phase III studies across a variety of indications and tumour types.

Lynparza is a registered trademark of AstraZeneca AB, used under license by AstraZeneca Canada Inc.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of primary and specialty care medicines that transform lives. Our primary focus is on three important areas of healthcare: Cardiovascular and Metabolic disease; Oncology; and Respiratory, Inflammation and Autoimmunity. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, we employ more than 675 employees across the country and our headquarters are located in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

ⁱ AstraZeneca Canada Inc., Lynparza^® (olaparib) Tablets Product Monograph. May 2018

ⁱⁱ Ibid.

ⁱⁱⁱ Ibid.

^iv Ibid.

^v AstraZeneca Canada Inc., Health Canada approves Lynparza™ for the Treatment of Ovarian Cancer in Patients with BRCA-Mutations. Newswire.ca. May 2016. Accessed April 11, 2018. https://www.newswire.ca/news-releases/health-canada-approves-Lynparza-for-the-treatment-of-ovarian-cancer-in-patients-with-brca-mutations-577929961.html

^vi Canadian Cancer Society. Breast Cancer Statistics. Accessed April 11, 2018. Available at: http://www.cancer.ca/en/cancer-information/cancer-type/breast/statistics/?region=bc

^vii Canadian Breast Cancer Foundation. Facts & Stats. Accessed April 11, 2018. Available at: http://www.cbcf.org/central/AboutBreastCancerMain/FactsStats/Pages/default.aspx

^viii Rethink Breast Cancer. Are you High Risk. Accessed April 11, 2018. Available at: https://rethinkbreastcancer.com/breast-health/what-you-need-to-know/are-you-high-risk/

^ix Ibid.

^x AstraZeneca Canada Inc., Lynparza^® (olaparib) Tablets Product Monograph. May 2018

^xi AstraZeneca Canada Inc., Health Canada approves Lynparza™ for the Treatment of Ovarian Cancer in Patients with BRCA-Mutations. Newswire.ca. May 2016. Accessed April 11, 2018. https://www.newswire.ca/news-releases/health-canada-approves-Lynparza-for-the-treatment-of-ovarian-cancer-in-patients-with-brca-mutations-577929961.html

SOURCE AstraZeneca

For further information: Stacey Brown, Senior Manager, Corporate Communications, AstraZeneca Canada, Tel: [phone] ext. 45733, Email: [e-mail]; Hibaq Ali, Manager, Integrated Media, Weber Shandwick Canada, Tel: [phone], Email: [e-mail]