Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a or Gene Alteration.

PURPOSE: or () 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 alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study.

METHODS: 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 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.

RESULTS: Efficacy and safety populations included 115 patients with a 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 alteration and for patients with a or alteration, while a higher PSA response rate was observed in patients with a alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients).

CONCLUSION: Rucaparib has antitumor activity in patients with mCRPC and a deleterious alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.