Untangling the PROfound Trial for Advanced Prostate Cancer: Is There Really a Role for Olaparib?

Abstract

The phase 3 PROfound trial led to the recent approval of the PARP inhibitor olaparib for men with metastatic castration-resistant prostate cancer and mutations in homologous recombination repair genes. We raise methodological concerns about the trial, including: a suboptimal control arm, problematic use of crossover, use of radiographic progression-free survival as the primary endpoint, and ambiguous benefit for patients with mutations in homologous recombination repair genes other than BRCA1, BRCA2, and ATM.