Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a <i>BRCA1</i> or <i>BRCA2</i> Gene Alteration.

Abstract

<i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA</i>) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a <i>BRCA</i> alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. We enrolled patients who progressed after one to two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious <i>BRCA</i> alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. Efficacy and safety populations included 115 patients with a <i>BRCA</i> alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic <i>BRCA</i> alteration and for patients with a <i>BRCA1</i> or <i>BRCA2</i> alteration, while a higher PSA response rate was observed in patients with a <i>BRCA2</i> alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). Rucaparib has antitumor activity in patients with mCRPC and a deleterious <i>BRCA</i> alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.