Health Canada Approves Lynparza in Combination with Abiraterone and Prednisone or Prednisolone for Patients with BRCA Mutated Metastatic Castration-Resistant Prostate Cancer
- Conditional approval based on data from Phase 3 PROpel trial
MISSISSAUGA, ON — Health Canada has granted a Notice of Compliance with Conditions (NOC/c) for Lynparza® (olaparib) in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious germline and/or somatic BRCA mutated metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated. BRCA mutation must be confirmed before Lynparza treatment is initiated.1
The conditional approval of Lynparza was granted based on the results from the PROpel Phase III clinical trial, which was published in the New England Journal of Medicine Evidence in June 2022. PROpel met its pre-specified primary endpoint. Subgroup analysis showed radiographic progression free survival (rPFS) improvement for Lynparza/abiraterone compared to placebo/abiraterone in mCRPC patients with a BRCA mutated mCRPC. For the BRCA subgroup, median rPFS was not calculable for the study arm at the time of the analysis because the median was not reached, compared to abiraterone/prednisone alone with rPFS 8.4 months (95% confidence interval [CI] 5.5 months-14.8 months). There was a reduced risk of radiological progression or death by 77% versus abiraterone/prednisone alone (based on a hazard ratio [HR] of 0.23 (95% confidence interval [CI] (0.12-0.43). At the time of the first interim analysis, overall survival showed a trend towards an improvement for Lynparza/abiraterone compared to placebo/abiraterone in mCRPC patients with a BRCA mutation. The safety and tolerability of Lynparza plus abiraterone in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse reactions of any grade (>10%) were anemia (46.0%), fatigue (37.2%) and nausea (28.1%).1,2
“Metastatic castration-resistant prostate cancer is a complex disease with a poor prognosis, making informed treatment decisions after a man’s initial diagnosis critical,” said Dr. Fred Saad, MD, FRCSC, Professor and Chairman of the Department of Surgery and Director of G-U Oncology at the University of Montreal. “Lynparza has demonstrated its clinical benefit in combination with a new generation hormonal agent in this setting, offering patients an effective and well tolerated new treatment option that can potentially reduce the risk of disease progression or death.”
Prostate cancer is the most common cancer among Canadian men (excluding non-melanoma skin cancers) and is the third leading cause of death from cancer. On average, 67 Canadian men will be diagnosed with prostate cancer every day, while 13 will die from it.3 Approximately 10–20% of patients with prostate cancer develop mCRPC within 5 years of follow-up after initial therapy. More than 80% of patients have bone metastases at castration-resistant prostate cancer (CRPC) diagnosis.4
“The high mortality rates associated with metastatic castration-resistant prostate cancer can invoke an added layer of fear and anxiety for men who have been diagnosed,” said Jackie Manthorne, President & CEO, Canadian Cancer Survivor Network. “We welcome the approval of new treatments like Lynparza that can help bring a renewed sense of hope to patients and their families.”
About the PROpel Phase III Clinical Trial
PROpel is a randomized, double-blind, placebo-controlled, multi-centre Phase III clinical trial testing the efficacy, safety, and tolerability of Lynparza in combination with abiraterone compared with placebo plus abiraterone in men with mCRPC. Men in both treatment groups also received either prednisone or prednisolone twice daily.1 The primary endpoint was rPFS and key secondary outcome measures included overall survival (OS), time to secondary progression or death, and time to first subsequent therapy.1,2
The safety and tolerability of Lynparza in combination with abiraterone was in line with that observed in prior clinical trials and the known profiles of the individual medicines. 1,2
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 use in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious germline and/or somatic BRCA mutated metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated, pending the results of studies to verify its clinical benefit. Patients should be advised of this conditional marketing authorization.
Lynparza is jointly developed and commercialized by AstraZeneca and Merck. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.
For more information about Lynparza, access the Canadian Product Monograph here.
The AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Rahway, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-
commercialise Lynparza, the world’s first PARP inhibitor, for multiple cancer types.
AstraZeneca is a global, science-led biopharmaceutical business whose innovative medicines are used by millions of patients worldwide. The company’s core areas of scientific focus are Oncology; Cardiovascular, Renal and Metabolic (CVRM); Rare Disease; Respiratory & Immunology; and Vaccine & Immune Therapies. AstraZeneca employs more than 1,300 people across Canada and recently announced a major expansion of its research footprint in Canada – including the expansion of its existing AstraZeneca R&D Hub and the creation of a new Alexion Development Hub for Rare Diseases. For more information, please visit the company’s website at www.astrazeneca.ca.
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable, and healthy future for all people and communities. For more information about our operations in Canada, visit www.merck.ca and connect with us on LinkedIn and Twitter @MerckCanada.
LYNPARZA® and the AstraZeneca logo are registered trademarks of AstraZeneca AB, used under license by AstraZeneca Canada Inc.
© 2023 AstraZeneca Canada Inc. and Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.
MERCK® is a registered trademark of Merck Sharp & Dohme LLC. Used under license.
1 Lynparza Product Monograph, July 10, 2023.
2 Clarke, Noel W et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence. 2022; 1(9). Available at: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200043. Accessed on June 26, 2023.
4 Merseburger, Axel S et al. Perspectives on Treatment of Metastatic Castration-Resistant Prostate Cancer.
Oncologist. 2013 May ; 18(5) : 558-567. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662847/#B6. Accessed on June 21, 2023.
Original source here.