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.
To present the final data from TRITON2.
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.
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.
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.
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.
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.
European urology. 2023 Jun 03 [Epub ahead of print]
Wassim Abida, David Campbell, Akash Patnaik, Alan H Bryce, Jeremy Shapiro, Richard M Bambury, Jingsong Zhang, John M Burke, Daniel Castellano, Albert Font, Vinod Ganju, Anne-Claire Hardy-Bessard, Ray McDermott, Brieuc Sautois, Dominique Spaeth, Eric Voog, Josep M Piulats, Elias Pintus, Charles J Ryan, Axel S Merseburger, Gedske Daugaard, Axel Heidenreich, Karim Fizazi, Andrea Loehr, Darrin Despain, Andrew D Simmons, Melanie Dowson, Jowell Go, Simon P Watkins, Simon Chowdhury
Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: ., Barwon Health, University Hospital Geelong, Geelong, Victoria, Australia., University of Chicago Comprehensive Cancer Center, Chicago, IL, USA., Mayo Clinic, Phoenix, AZ, USA., Cabrini Hospital, Malvern, Victoria, Australia., Cork University Hospital, Wilton, Cork, Ireland., H. Lee Moffitt Cancer Center, Tampa, FL, USA., Rocky Mountain Cancer Centers and US Oncology Research, Denver, CO, USA., University Hospital 12 de Octubre, Madrid, Spain., Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain., Hudson Institute of Medical Research, Clayton, Victoria, Australia., CARIO HPCA, Plérin, France., Adelaide and Meath Hospital (Incorporating the National Children's Hospital), Dublin, Ireland., Medical Oncology, University Hospital of Liège, CHU Sart Tilman, Liège, Belgium., Centre d'Oncologie de Gentilly, Nancy, France., Clinique Victor Hugo Centre Jean Bernard, Le Mans, France., Institut Català d'Oncologia, Barcelona, Spain., Guy's & St Thomas' NHS Foundation Trust Hospital, London, UK., University of Minnesota, Minneapolis, MN, USA., University Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany., Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Universitätsklinikum Köln, Cologne, Germany; Department of Urology, Medical University Vienna, Vienna, Austria., Institut Gustave Roussy, University of Paris Saclay, Villejuif Cedex, France., Clovis Oncology, Inc., Boulder, CO, USA., Clovis Oncology UK, Ltd., Cambridge, UK.