Background: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration. Objective: To present the final data from TRITON2. Design, setting, and participants: TRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR; as per the modified Response Evaluation Criteria in Solid Tumor Version 1.1/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease by independent radiology review [IRR]); prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) was a key secondary endpoint. Results and limitations: As of July 27, 2021 (study closure), TRITON2 had enrolled 277 patients, grouped by mutated gene: BRCA (n = 172), ATM (n = 59), CDK12 (n = 15), CHEK2 (n = 7), PALB2 (n = 11), or other DDR gene (Other; n = 13). ORR by IRR was 46% (37/81) in the BRCA subgroup (95% confidence interval [CI], 35–57%), 100% (4/4) in the PALB2 subgroup (95% CI, 40–100%), and 25% (3/12) in the Other subgroup (95% CI, 5.5–57%). No patients within the ATM, CDK12, or CHEK2 subgroups had an objective response by IRR. PSA50 response rates (95% CI) in the BRCA, PALB2, ATM, CDK12, CHEK2, and Other subgroups were 53% (46–61%), 55% (23–83%), 3.4% (0.4–12), 6.7% (0.2–32%), 14% (0.4–58%), and 23% (5.0–54%), respectively. Conclusions: The final TRITON2 results confirm the clinical benefit and manageable safety profile of rucaparib in patients with mCRPC, including those with an alteration in BRCA or select non-BRCA DDR gene. Patient summary: Almost half of TRITON2 patients with BRCA-mutated metastatic castration-resistant prostate cancer had a complete or partial tumor size reduction with rucaparib; clinical benefits were also observed with other DNA damage repair gene alterations.
Bibliographical noteFunding Information:
Acknowledgments: The authors thank Dr. Nicholas J. Vogelzang for his valuable contributions to this study, including the provision of study materials and data collection/assembly. This study was funded by Clovis Oncology, Inc. Medical writing and editorial support were funded by Clovis Oncology, Inc., and were provided by Sachi Yim, PhD, and Kathleen Blake, PhD, of Ashfield MedComms, an Inizio company.
Funding/Support and role of the sponsor: This work was supported by Clovis Oncology Inc; supported in part by the National Cancer Institute (NCI) Cancer Center Support (grant number P30-CA008748), NCI Prostate Specialized Program of Research Excellence (SPORE; grant number P50-CA092629-16), Department of Defense Prostate Cancer Research Program (grant number W81XWH-17-1-0124), and a Prostate Cancer Foundation Young Investigator Award (to Wassim Abida); and supported in part by a Prostate Cancer Foundation Challenge Award and NCI Prostate SPORE grant (no. P50-CA180995; to Akash Patnaik).
- DNA damage repair gene alteration
- Metastatic castration-resistant prostate cancer
- Poly(ADP-ribose) polymerase inhibitor
PubMed: MeSH publication types
- Clinical Trial, Phase II
- Journal Article
- Research Support, U.S. Gov't, Non-P.H.S.
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural