This article summarizes the US Food and Drug Administration (FDA) review of the data leading to approval of olaparib plus abiraterone for the treatment of patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.
Approval was based on the results from PROpel, a double-blind trial that randomly assigned 796 patients with mCRPC to abiraterone plus prednisone or prednisolone with either olaparib or placebo. The primary end point was radiographic progression-free survival (rPFS) per investigator assessment.
There was a statistically significant improvement in rPFS for olaparib plus abiraterone versus placebo plus abiraterone, with a median rPFS of 25 versus 17 months and a hazard ratio (HR) of 0.66 (95% CI, 0.54 to 0.81) in the intention-to-treat population. In an exploratory analysis of the subgroup of 85 patients with BRCAm mCRPC, the HR for rPFS was 0.24 (95% CI, 0.12 to 0.45) and the HR for overall survival (OS) was 0.30 (95% CI, 0.15 to 0.59). In an exploratory analysis of the subgroup of 711 patients without an identified BRCA mutation, the HR for rPFS was 0.77 (95% CI, 0.63 to 0.96) and the HR for OS was 0.92 (95% CI, 0.74 to 1.14). Adding olaparib to abiraterone resulted in increased toxicity, including anemia requiring transfusion in 18% of patients.
In patients with mCRPC, efficacy of the combination of olaparib plus abiraterone was primarily attributed to the treatment effect in the BRCAm subgroup, the indicated population for the approval. For patients without BRCAm, the FDA determined that the modest rPFS improvement, combined with clinically significant toxicities, did not demonstrate a favorable risk/benefit assessment.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Dec 21 [Epub ahead of print]
Jaleh Fallah, Jianjin Xu, Chana Weinstock, Michael H Brave, Erik Bloomquist, Mallorie H Fiero, Timothy Schaefer, Anand Pathak, Abdelrahmman Abukhdeir, Vishal Bhatnagar, Haw-Jyh Chiu, Tiffany Ricks, Christy John, Salaheldin Hamed, Christal Lee, William F Pierce, Shyam Kalavar, Reena Philip, Shenghui Tang, Laleh Amiri-Kordestani, Richard Pazdur, Paul G Kluetz, Daniel Suzman
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD., Center for Devices and Radiological Health (CDRH), US Food and Drug Administration, Silver Spring, MD., Oncology Center of Excellence (OCE), US Food and Drug Administration, Silver Spring, MD.