Lynparza reduced the risk of death by 31% in BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer in phase III PROfound trial. AstraZeneca + Merck Inc.

Final results from the Phase III PROfound trial showed AstraZeneca and MSD’s Lynparza (olaparib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus enzalutamide or abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 or ATM gene mutations, a subpopulation of homologous recombination repair (HRR) gene mutations. Patients had progressed on prior treatment with new hormonal agent (NHA) treatments (i.e. enzalutamide and abiraterone). Prostate cancer is the second-most common type of cancer in men, with an estimated 1.3 million new patients diagnosed worldwide in 2018. Approximately 20-30% of men with mCRPC have an HRR gene mutation. In the key secondary endpoint of OS, Lynparza reduced the risk of death by 31% versus enzalutamide or abiraterone (based on a hazard ratio [HR] of 0.69; 95% confidence interval [CI] 0.50-0.97; p=0.0175). Median OS was 19.1 months for Lynparza versus 14.7 months for enzalutamide or abiraterone, despite 66% of men on NHA treatments had crossed over to receive treatment with Lynparza following disease progression. An exploratory analysis also showed a non-statistically significant improvement in OS in the overall trial population of men with HRR gene mutations (BRCA1/2, ATM, CDK12 and 11 other HRRm genes), reducing the risk of death by 21% with Lynparza versus enzalutamide or abiraterone (based on a HR of 0.79; 95% CI 0.61-1.03). Median OS was 17.3 months versus 14.0 months for enzalutamide or abiraterone.