Lynparza receives Health Canada approval as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer

First and only approved medicine targeting germline BRCA mutations in high-risk early breast cancer

MISSISSAUGA, ON, Aug. 11, 2022 /CNW/ - Health Canada has granted a Notice of Compliance with Conditions (NOC/c) for Lynparza^® (olaparib) for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.¹ Patients must have confirmation of a germline BRCA mutation before Lynparza treatment is initiated.¹

This approval was granted under Health Canada’s accelerated review pathway and based on results from the OlympiA Phase III trial,¹ presented during the 2021 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine. The OlympiA trial demonstrated a reduction in the risk of invasive breast cancer recurrences, second cancers or death by 42 per cent versus placebo (based on a hazard ratio [HR] of 0.58; 95% confidence interval [CI] 0.41-0.82; p<0.0001).¹

“Although most HER2-negative early breast cancers now have excellent outcomes, the risk of disease recurrence for persons with high-risk breast cancers and BRCA mutations remains unacceptably high, with a significant potential to advance to advanced disease, where a cure is no longer an option,” said Dr. Karen Gelmon, Professor of Medicine, University of British Columbia and Medical Oncologist, BC Cancer. “Today’s approval of olaparib is an important step forward, offering these patients a much-needed option that can improve survival for persons with high-risk early breast cancer. It also stresses the importance of BRCA testing as soon as possible after diagnosis to identify eligible patients.”

In Canada, it is estimated that 94 per cent of all breast cancers are detected at an early stage.² Despite advances in the treatment of early breast cancer, up to 30 per cent of patients with high-risk clinical and/or pathologic features recur within the first few years.³ The risk is particularly high for patients with germline BRCA mutations, who are more likely to be diagnosed at a younger age than those without these mutations.²

“This approval is fantastic news for the many women with high-risk early breast cancer who live with the ongoing fear of recurrence and what that means for their future,” said Cathy Ammendolea, Chair of the Board, Canadian Breast Cancer Network. “New treatment options can provide hope for patients and their families, and we look forward to Canadian women having access to this treatment.”

“Hereditary breast cancer is often diagnosed at a younger age and Rethink has supported and advocated for young people with breast cancer for more than 20 years. Facing their mortality at a young age, they want what all cancer patients want – care that will lead to the best possible outcome, including reducing their future cancer risk,” said MJ DeCoteau, Founder and Executive Director of Rethink Breast Cancer. “They want to survive, and eventually thrive, and now patients with a BRCA-mutated breast cancer will have a treatment that is shown to help them do just that.”

OlympiA is a Phase III, double-blind, placebo-controlled, multicentre trial testing the efficacy and safety of Lynparza as adjuvant treatment in patients with gBRCAm HER2-negative high-risk early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.¹ The primary endpoint was invasive disease-free survival (iDFS), and key secondary outcome measures include distant disease-free survival (DDFS) and overall survival (OS).¹

In the key secondary endpoint, results showed an improvement of distant disease-free survival (DDFS) in the intention to treat (ITT) population, where Lynparza reduced the risk of distant disease recurrence or death by 43 per cent (based on a HR of 0.57 (99.5% CI:0.39-0.83; P < 0.001).¹ Interim overall survival (8% maturity, DCO 27 March 2020) did not meet statistical significance.¹

The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.¹

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.⁴

When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including Lynparza.⁵

Lynparza was the first oral (PARP) inhibitor approved in Canada. Lynparza exploits tumour DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2, to selectively kill cancer cells.¹ Lynparza is the only PARP inhibitor currently approved in multiple tumour types in Canada including breast, ovarian, pancreatic and prostate cancers.

Lynparza has been issued conditional marketing authorization for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy pending the results of studies to verify its clinical benefit. Patients should be advised of this conditional marketing authorization.

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and Biopharmaceuticals, including Cardiovascular, Renal & Metabolism (CVRM), and Respiratory & Immunology. The company employs more than 1,200 people across Canada, including 700 employees at our head office and clinical research hub in Mississauga, Ontario. For more information, please visit the company’s website at www.astrazeneca.ca.

REFERENCES

¹ Lynparza Product Monograph, July 27, 2022.

² S, Masoud H, Weir HK, et al. Cancer in Canada: Stage at diagnosis. (1209-1367 (Electronic).

³ Colleoni M, et al. Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V. J Clin Oncol. 2016 Mar 20; 34(9):927-935.

⁴ Canadian Breast Cancer Network, BRCA Gene Mutations. Available at: https://cancer.ca/en/cancer-information/cancer-types/breast/risks#ci_BRCA_gene_mutations_10_185_04. Accessed July 12, 2022.

⁵ Roy R, et al. BRCA1 and BRCA2: Different Roles in a Common Pathway of Genome Protection. Nat Rev Cancer. 2016;12(1):68-78.

SOURCE AstraZeneca Canada Inc.