Proof is in the PARP.
Top Line: Do PARP inhibitors improve survival in men with metastatic prostate cancer and DNA repair defects?
The Study: Initial results of the PROfound trial showed that men with metastatic castration resistant prostate cancer (mCRPC) and associated defects in DNA repair genes benefited from olaparib (PARP inhibitor) after progressing on second-line androgen axis inhibition. Overall survival results were immature at that time, but they aren’t anymore. As a reminder, patients in PROfound were put in two different cohorts: cohort A included those with a BRCA1, BRCA1, or ATM alteration while cohort B included alterations in a broader list of DNA repair genes. In cohort A, olaparib significantly prolonged median overall survival 14.7→ 19.1 months (HR 0.69). The difference in the overall population was encouraging (14→ 17.3 months), but it was driven by the BRCA/ATM group as there was no significant improvement among cohort B. Two-thirds of patients in the control arm crossed-over to receive olaparib. Accounting for that cross-over demonstrated an even bigger magnitude of benefit in cohort A (HR 0.42).TBL: PARP inhibition with olaparib prolongs survival in men with mCRPC and BRCA/ATM mutations after progression on abiraterone or enzalutamide. | Hussain, N Engl J Med 2020 (ESMO 2020)