Poly(ADP-ribose) polymerase (PARP) inhibitors have been previously shown to improve the outcomes of patients with BRCA-mutant prostate cancer. Now, data from a phase II study demonstrate that the PARP inhibitor olaparib, in combination with abiraterone, provides benefit even in the absence of homologous recombination (HRR) deficiency. 142 patients were randomly assigned to receive abiraterone plus olaparib or abiraterone plus placebo regardless of HRR status. Patients receiving olaparib plus abiraterone had significantly improved median radiographic progression-free survival relative to those in the abiraterone plus placebo group (13.8 months versus 8.2 months; HR 0.65, 95% CI 0.44–0.97; P = 0.034). Patients in the olaparib group had an increased risk of grade ≥3 adverse events (41% versus 27%); however, grade 1–2 adverse events were more frequent in patients receiving abiraterone alone.
Clarke, N. et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. https://doi.org/10.1016/S1470-2045(18)30365-6 (2018)
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Sidaway, P. PARP inhibitors synergize with abiraterone. Nat Rev Clin Oncol 15, 532 (2018). https://doi.org/10.1038/s41571-018-0060-9