Rucaparib in Men with Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration

TRITON2 investigators

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3763-3772
Number of pages10
JournalJournal of Clinical Oncology
Issue number32
StatePublished - Nov 10 2020

Bibliographical note

Funding 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.).

Funding Information:
The authors thank Cheryl Chun and Vivian Chen of Clovis Oncology for assistance in manuscript preparation. Medical writing and editorial support funded by Clovis Oncology were provided by Nathan Yardley and Frederique H. Evans of Ashfield Healthcare Communications.

PubMed: MeSH publication types

  • Journal Article

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