European urology
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The PROfound trial evaluated the PARP inhibitor olaparib in metastatic castration-resistant prostate cancers harboring alterations in BRCA1/2 and ATM (cohort A) and in 12 other homologous recombination repair genes (cohort B). Olaparib led to more objective responses and longer radiographic progression-free survival than the control in cohort A and when cohorts A and B were combined. The efficacy of olaparib in cohort B was a secondary objective prespecified in the trial protocol but was not reported. ⋯ These results are in strong contrast to cohort A. PATIENT A large clinical study concluded that treatment with the PARP inhibitor olaparib benefits men with metastatic castration-resistant prostate cancer whose tumors harbor alterations in 15 different DNA repair genes. In contrast to the group dominated by BRCA alterations, any potential benefit from olaparib was considerably less, if present at all, for men with prostate cancers harboring one of the 12 other, non-BRCA DNA repair alterations.