• Karim Fizazi, Josep M Piulats, M Neil Reaume, Peter Ostler, Ray McDermott, Joel R Gingerich, Elias Pintus, Srikala S Sridhar, Richard M Bambury, Urban Emmenegger, Henriette Lindberg, David Morris, Franco Nolè, John Staffurth, Charles Redfern, María I Sáez, Wassim Abida, Gedske Daugaard, Axel Heidenreich, Laurence Krieger, Brieuc Sautois, Andrea Loehr, Darrin Despain, Catherine A Heyes, Simon P Watkins, Simon Chowdhury, Charles J Ryan, Alan H Bryce, and TRITON3 Investigators.
• From Gustave Roussy Institute, Paris-Saclay University, Villejuif, France (K.F.); Institut Català d'Oncologia-Bellvitge Institute for Biomedical Research -CiberOnc, Barcelona (J.M.P.), and the Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga (M.I.S.) - both in Spain; the Ottawa Hospital Research Institute, Ottawa (M.N.R.), CancerCare Manitoba, Winnipeg (J.R.G.), and Princess Margaret Cancer Centre (S.S.S.) and Odette Cancer Centre, Sunnybrook Health Sciences Centre (U.E.), Toronto - all in Canada; Mount Vernon Cancer Centre, Northwood (P.O.), Guy's Hospital (E.P.) and Guy's Hospital and Sarah Cannon Research Institute (S.C.), London, Velindre University NHS Trust, Cardiff (J.S.), and Clovis Oncology UK, Cambridge (C.A.H., S.P.W.) - all in the United Kingdom; St. Vincent's University Hospital and Cancer Trials Ireland, Dublin (R.M.), and Cork University Hospital, Wilton (R.M.B.) - both in Ireland; Herlev University Hospital, Herlev (H.L.), and Copenhagen University Hospital, Rigshospitalet, Copenhagen (G.D.) - both in Denmark; Urology Associates, Nashville (D.M.); European Institute of Oncology IRCCS, Milan (F.N.); Sharp HealthCare, San Diego, CA (C.R.); Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York (W.A.); Universitätsklinikum Köln, Cologne, Germany (A.H.); Medical University of Vienna, Vienna (A.H.); Genesis Care, North Shore, Sydney (L.K.); University Hospital of Liège, CHU Sart-Tilman, Liège, Belgium (B.S.); Clovis Oncology, Boulder, CO (A.L., D.D.); the University of Minnesota, Minneapolis (C.J.R.); and Mayo Clinic, Phoenix, AZ (A.H.B.).
• N. Engl. J. Med. 2023 Feb 23; 388 (8): 719732719-732.

BackgroundIn a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with a deleterious BRCA alteration. Data are needed to confirm and expand on the findings of the phase 2 study.MethodsIn this randomized, controlled, phase 3 trial, we enrolled patients who had metastatic, castration-resistant prostate cancer with a BRCA1, BRCA2, or ATM alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI). We randomly assigned the patients in a 2:1 ratio to receive oral rucaparib (600 mg twice daily) or a physician's choice control (docetaxel or a second-generation ARPI [abiraterone acetate or enzalutamide]). The primary outcome was the median duration of imaging-based progression-free survival according to independent review.ResultsOf the 4855 patients who had undergone prescreening or screening, 270 were assigned to receive rucaparib and 135 to receive a control medication (intention-to-treat population); in the two groups, 201 patients and 101 patients, respectively, had a BRCA alteration. At 62 months, the duration of imaging-based progression-free survival was significantly longer in the rucaparib group than in the control group, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval [CI], 0.36 to 0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001 for both comparisons). In an exploratory analysis in the ATM subgroup, the median duration of imaging-based progression-free survival was 8.1 months in the rucaparib group and 6.8 months in the control group (hazard ratio, 0.95; 95% CI, 0.59 to 1.52). The most frequent adverse events with rucaparib were fatigue and nausea.ConclusionsThe duration of imaging-based progression-free survival was significantly longer with rucaparib than with a control medication among patients who had metastatic, castration-resistant prostate cancer with a BRCA alteration. (Funded by Clovis Oncology; TRITON3 ClinicalTrials.gov number, NCT02975934.).Copyright © 2023 Massachusetts Medical Society.

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