PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations
In men with metastatic castration-resistant prostate cancer carrying BRCA1, BRCA2 or ATM alterations who had progressed on hormonal therapy, the PARP inhibitor olaparib delayed progression and lengthened survival compared with another hormonal agent.
Overview
Phase 3 trial of 387 men with metastatic castration-resistant prostate cancer progressing on enzalutamide or abiraterone, with alterations in BRCA1, BRCA2 or ATM (cohort A) or 12 other homologous recombination genes (cohort B), randomised 2:1 to olaparib or physician's choice of enzalutamide or abiraterone.
In cohort A median progression-free survival was 7.4 versus 3.6 months (hazard ratio 0.34) and median overall survival 19.1 versus 14.7 months (hazard ratio 0.69 despite crossover); benefit was driven mainly by BRCA2.
- Cohort A: median progression-free survival 7.4 vs 3.6 months; hazard ratio 0.34.
- Cohort A: median overall survival 19.1 vs 14.7 months; hazard ratio 0.69.
Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
- Benefit in ATM and the cohort B genes was weak or absent.
- The comparator, a second hormonal agent, has limited activity after progression on the first.
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