Excitement over the positive progression-free survival (PFS) data reported last year in the PROfound trial continues, with final overall survival (OS) data presented today at ESMO Virtual Congress 2020 (Abstract 610O) showing significant benefits with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in men with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1, BRCA2 or ATM mutations.
PROfound is a prospective, multicentre, randomised, open-label, phase III study evaluating the efficacy and safety of olaparib (300 mg twice daily) versus control (physician’s choice of enzalutamide [160 mg/day] or abiraterone [1000 mg/day]) in 387 patients with mCRPC who had progressed on a new hormonal agent and had a tumour mutation in one of 15 genes that have a role in the homologous recombination repair (HRR) pathway. OS was analysed as a prespecified key secondary endpoint in Cohort A, which comprised patients with alterations in BRCA1, BRCA2 or ATM, and the overall population.
At the March 2020 data cut-off, median OS was significantly longer with olaparib than control treatment in Cohort A (19.1 months versus 14.7 months; hazard ratio [HR] 0.69; 95% CI, 0.50–0.97; p=0.0175) with a trend towards improvement in the overall population (17.3 months versus 14.0 months; HR 0.79; 95% CI, 0.61–1.03; nominal p=0.0515). This is despite approximately two-thirds of patients in the control arm crossing over to olaparib following radiographic disease progression. The long-term safety of olaparib was as expected from previous studies of olaparib.
These final OS data from the PROfound trial, alongside the positive PFS data, are very likely to alter the treatment paradigm for patients with mCRPC who can be selected based on their BRCA1, BRCA2 or ATM status. It is anticipated that the recent US FDA approval granted to olaparib for the treatment of patients with HRR gene-mutated mCRPC who have progressed following treatment with enzalutamide or abiraterone will be followed by EMA approval in the near future.
Abstract and session details
- De Bono JS et al. Final overall survival (OS) analysis of PROfound: Olaparib vs physician’s choice of enzalutamide or abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations. ESMO Virtual Congress 2020, Abstract 610O
Proffered Paper - Presidential Symposium II, 20.09.2020, h. 18:30 – 20:25, Channel 1