Canadian authorities have approved Lynparza (olaparib) as an oral treatment for people with metastatic castration-resistant prostate cancer (mCRPC) who carry mutations in BRCA or ATM genes, both of which are involved in DNA repair.
The approval, granted under priority review, is specifically indicated for patients who progressed after treatment with new forms of hormone therapy, such as Xtandi (enzalutamide) or Zytiga (abiraterone acetate). It makes Lynparza the first PARP inhibitor approved for prostate cancer in Canada.
“The risk of developing prostate cancer is significantly higher for carriers of the BRCA or ATM-gene mutation, which affects roughly 10 per cent of men living with mCRPC,” Kim Chi, MD, at the University of British Columbia, said in a press release.
“This new approval offers patients a much-needed new treatment option, and also reinforces the importance of BRCA and ATM testing,” he said.
Lynparza, jointly developed by AstraZeneca and MSD (known as Merck in North America), works by blocking the activity of PARP, an enzyme that is involved in DNA repair. The therapy renders cancer cells more vulnerable to DNA damage, which reduces their ability to grow and survive.
This oral therapy is approved in the U.S. for men with mCRPC carrying mutations in their BRCA and ATM genes and also in the European Union for men with mCRPC and BRCA mutations.
Canada’s approval was based on data from the PROfound Phase 3 clinical trial (NCT02987543), specifically from the 245 participants with mutations in the BRCA1, BRCA2, or ATM genes.
Participants had experienced disease progression while receiving treatment with newer forms of hormone therapy, and were assigned randomly to receive Lynparza or an investigators’ choice of hormone therapies — Xtandi or Zytiga plus the corticosteroid prednisone.
The trial’s main goal was to assess whether Lynparza outperformed hormone therapy at delaying disease progression — assessed via regular imaging scans — or death from any cause.
Results showed that participants with BRCA or ATM mutations who received Lynparza lived significantly longer without disease progression — a median of 7.4 months vs. 3.6 months on hormone therapies, corresponding to a 66% decrease in the risk of disease worsening or death.
These patients also lived longer than those given hormone therapy — median 19.1 months vs. 14.7 months — representing a reduction by 31% in the risk of death.
The therapy’s safety profile was consistent with that from previous studies, with the exception of blood clots, which were detected in 7% of patients given Lynparza and in 3.1% of patients given hormone therapies.
The rate of pulmonary embolism also was higher in patients given Lynparza (6% vs 0.8%) but, based on available clinical data, no link has been established between Lynparza and these events.
“We are thrilled to hear about this new indication for patients with BRCA or ATM-mutated mCRPC,” said Jackie Manthorne, president and CEO, Canadian Cancer Survivor Network. “This aggressive form of prostate cancer can have a devastating impact on patients and families, but this new treatment option is providing much-needed hope for better outcomes.”