AstraZeneca plc (LON:AZN) and MSD’s Lynparza (olaparib) has been granted conditional approval in China to treat adult patients with germline or somatic BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following treatment that included a new hormonal agent (abiraterone, enzalutamide).
In China, prostate cancer is the sixth most prevalent cancer in men, with approximately 115,000 new patients diagnosed each year and about 7% have germline BRCA mutations.1,2 Prostate cancer patients with these mutations are more likely to have poorer outcomes than those without the mutations.3 Around 70% of prostate cancer patients in China have advanced disease at the time of diagnosis, and for those with mCRPC, the median survival is less than two years.4,5
The approval by China’s National Medical Products Administration was based on a subgroup analysis of the PROfound Phase III trial, which showed that Lynparza demonstrated a substantial improvement in radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone or enzalutamide in men with BRCA1/2 mutations. Continued approval is contingent upon verification and description of clinical benefit in a planned bridging trial with Chinese patients.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “This approval begins a new era of precision medicine for patients in China with advanced prostate cancer who have historically had a poor prognosis and few treatment options. Lynparza more than tripled radiographic progression-free survival in the PROfound trial and is the only PARP inhibitor to show an overall survival benefit compared to treatment with new hormonal agents for men with BRCA-mutated metastatic castration-resistant prostate cancer.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “The approval underscores the critical importance of BRCA testing in men with prostate cancer. We are proud to provide a new personalised treatment option for men with this devastating disease in China, and we will continue to collaborate with the Chinese government and healthcare organisations to bring Lynparza to patients who need it.”
The subgroup analysis from the PROfound Phase III trial showed Lynparza reduced the risk of disease progression or death by 78% (based on a hazard ratio [HR] of 0.22, 95% confidence interval [CI] 0.15-0.32; nominal p<0.0001) and improved rPFS to a median of 9.8 months versus 3.0 with abiraterone or enzalutamide in men with mCRPC with BRCA1/2 mutations. In addition, Lynparza reduced the risk of death by 37% (HR of 0.63, 95% CI 0.42-0.95) with median OS of 20.1 months versus 14.4 with abiraterone or enzalutamide.
The primary results and OS results from the PROfound Phase III trial were published in The New England Journal of Medicine.
Lynparza is approved in the US to treat men with homologous recombination repair gene-mutated (HRRm) mCRPC and in the EU, Japan and several other countries for BRCA-mutated mCRPC patients based on the PROfound Phase III trial. In addition, regulatory reviews are ongoing in other countries around the world.
AstraZeneca and MSD are testing Lynparza in additional trials in metastatic prostate cancer, including the ongoing PROpel Phase III trial of Lynparza as a 1st-line treatment for patients with mCRPC in combination with abiraterone versus abiraterone alone. Results are anticipated in the second half of 2021.
