Lynparza approved in the EU for the treatment of BRCA- mutated metastatic castration-resistant prostate cancer

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in the European Union (EU) for patients with metastatic castration-resistant prostate cancer (mCRPC) with breast cancer susceptibility gene 1/2 (BRCA1/2) mutations, a subpopulation of homologous recombination repair (HRR) gene mutations.

Prostate cancer is the second-most common type of cancer in men, with an estimated 1.3 million patients diagnosed worldwide in 2018. Approximately 12% of men with mCRPC have a BRCA mutation.

The approval by the European Commission was based on a subgroup analysis of the PROfound Phase III trial which showed Lynparza demonstrated a substantial improvement in radiographic progression-free survival (rPFS) and overall survival (OS) versus enzalutamide or abiraterone in men with BRCA1/2 mutations.

Lynparza is the first and only PARP inhibitor approved in the EU in biomarker-selected advanced prostate cancer. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in September 2020.

Johann de Bono, one of the principal investigators of the PROfound Phase III trial, Head of Drug Development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said: “This approval in the EU is a landmark moment that begins a new era of precision medicine in prostate cancer. Lynparza now provides a targeted treatment option at a molecular level to patients with advanced prostate cancer who have historically poor prognosis and few treatment options.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Lynparza more than tripled radiographic progression-free survival and is the only PARP inhibitor to show an overall survival benefit versus certain new hormonal agents for men with BRCA-mutated metastatic castration-resistant prostate cancer. This approval means BRCA testing should now become a critical step in the diagnosis and determination of treatment for men with advanced prostate cancer in the EU.”

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “The PROfound Phase III trial showed Lynparza provided a clinical benefit for men living with BRCA1/2-mutated metastatic castration-resistant prostate cancer, offering an important option to improve overall survival for these patients in the EU. MSD, along with our collaborator AstraZeneca, looks forward to making this targeted treatment available for patients across the EU as quickly as possible.”

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 enzalutamide or abiraterone in men with mCRPC with BRCA1/2 mutations. Lynparza reduced the risk of death by 37% (based on a HR of 0.63, 95% CI 0.42-0.95) with median OS of 20.1 months versus 14.4 with enzalutamide or abiraterone.

The primary results and overall survival results from the PROfound Phase III trial were published in The New England Journal of Medicine earlier this year.

The full EU approved indication for Lynparza is for the treatment of adult patients with mCRPC and BRCA1/2 mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.

Lynparza was approved in the US for men with HRR gene-mutated mCRPC in May 2020 based on the PROfound Phase III trial. Regulatory reviews are ongoing in other countries around the world.

AstraZeneca and MSD are exploring additional trials in metastatic prostate cancer including the ongoing PROpel Phase III trial testing Lynparza as a 1st-line treatment for patients with mCRPC in combination with abiraterone versus abiraterone alone. Data are anticipated in the second half of 2021.