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.
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.
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).
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.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 Aug 14 [Epub ahead of print]
Wassim Abida, Akash Patnaik, David Campbell, Jeremy Shapiro, Alan H Bryce, Ray McDermott, Brieuc Sautois, Nicholas J Vogelzang, Richard M Bambury, Eric Voog, Jingsong Zhang, Josep M Piulats, Charles J Ryan, Axel S Merseburger, Gedske Daugaard, Axel Heidenreich, Karim Fizazi, Celestia S Higano, Laurence E Krieger, Cora N Sternberg, Simon P Watkins, Darrin Despain, Andrew D Simmons, Andrea Loehr, Melanie Dowson, Tony Golsorkhi, Simon Chowdhury, TRITON2 investigators
Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY., Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL., Barwon Health, University Hospital Geelong, Geelong, VIC, Australia., Medical Oncology, Cabrini Hospital, Malvern, VIC, Australia., Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ., Genitourinary Oncology, Adelaide and Meath Hospital (incorporating the National Children's Hospital), Dublin, Ireland., Medical Oncology, University Hospital of Liège, CHU Sart Tilman, Liège, Belgium., Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV., Medical Oncology, Cork University Hospital, Wilton, Cork, Ireland., Medical Oncology, Clinique Victor Hugo Centre Jean Bernard, Le Mans, France., Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, FL., Medical Oncology, Institut Català d'Oncologia, Barcelona, Spain., Department of Medicine, University of Minnesota, Minneapolis, MN., Department of Urology, Lübeck University Hospital, Lübeck, Germany., Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Department of Urology, Universitätsklinikum Köln, Cologne, Germany., Medical Oncology, Institut Gustave Roussy, University of Paris Saclay, Villejuif Cedex, France., Department of Medicine, Division of Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA., Oncology, Northern Cancer Institute, St Leonards, Sydney, NSW, Australia., Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY., Clinical Science, Clovis Oncology UK, Cambridge, United Kingdom., Biostatistics, Clovis Oncology, Boulder, CO., Translational Medicine, Clovis Oncology, Boulder, CO., Study Operations, Clovis Oncology UK, Cambridge, United Kingdom., Clinical Development, Clovis Oncology, Boulder, CO., Medical Oncology, Guy's Hospital, London, United Kingdom.