PARP Inhibition in Men With Resistant Prostate Cancer
Posted: Tuesday, June 9, 2020
According to Johann de Bono, MB, ChB, PhD, of the Institute of Cancer Research and Royal Marsden Hospital, London, and a host of multinational colleagues, patients with metastatic castration-resistant prostate cancer who possess mutations of some homologous recombination–repair genes appear to derive a progression-free survival benefit from treatment with the PARP inhibitor olaparib. However, longer follow-up is necessary to confirm a conclusive improvement in survival. The findings of the PROfound phase III trial were published in The New England Journal of Medicine.
“Our findings show that olaparib…can outperform targeted hormone treatments in some men with advanced prostate cancer,” Dr. de Bono commented in a Prostate Cancer Foundation press release. “Next, we will be assessing how we can combine olaparib with other treatments.”
Patients with metastatic castration-resistant disease who experienced disease progression while being treated with either enzalutamide or abiraterone were enrolled. Cohort A comprised 245 patients who possessed mutations in BRCA1, BRCA2, or ATM. A total of 142 patients with mutations in any of 12 other prespecified homologous recombination–repair genes were assigned to cohort B. Men in each cohort were randomly assigned in a 2:1 ratio to receive olaparib or a control treatment of either enzalutamide or abiraterone.
Based upon an analysis of cohort A, the investigators reported an increased median overall survival in the experimental group (18.5 months), compared with the control group (15.1 months). Of note, the risk of death and disease progression was 66% lower in the experimental group. The median lengths of imaging-based progression- free survival in the experimental and control groups of cohort A were 7.4 months and 3.6 months, respectively (P < .001). After combining data from both cohorts, the investigators observed a significantly longer progression-free survival with olaparib than without (median, 5.8 vs. 3.5 months; P < .001).
Disclosure: For full disclosures of the study authors, visit www.nejm.org.