PURPOSE BRCA1 or BRCA2 (BRCA) 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 BRCA 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 BRCA 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 BRCA 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 BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 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 BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.
Bibliographical noteFunding Information:
Funded by Clovis Oncology; supported in part by the National Cancer Institute (NCI) Cancer Center Support Grant No. P30-CA008748, NCI Prostate Specialized Program of Research Excellence (SPORE) Grant No. P50-CA092629-16, Department of Defense Prostate Cancer Research Program Grant No. W81XWH-17-1-0124, and a Prostate Cancer Foundation Young Investigator Award (W.A.); and supported in part by a Prostate Cancer Foundation Challenge Award and NCI Prostate SPORE Grant No. P50-CA180995 (A.P.).
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.