rucaparib; Indoles; Male; Humans; Indoles/therapeutic use; Progression-Free Survival; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Prostatic Neoplasms, Castration-Resistant/drug therapy; Physicians; General Medicine
Abstract :
[en] [en] BACKGROUND: In 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.
METHODS: In 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.
RESULTS: Of 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.
CONCLUSIONS: The 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.).
Disciplines :
Oncology
Author, co-author :
Fizazi, Karim; Gustave Roussy Institute, Paris-Saclay University, Villejuif, France
Piulats, Josep M; Institut Català d'Oncologia-Bellvitge Institute for Biomedical Research -CiberOnc, Barcelona, Spain
Reaume, M Neil; The Ottawa Hospital Research Institute, Ottawa, Canada,
Ostler, Peter; Mount Vernon Cancer Centre, Northwood (P.O.), United Kingdom
McDermott, Ray; St. Vincent's University Hospital and Cancer Trials Ireland, Dublin, Ireland
Gingerich, Joel R; CancerCare Manitoba, Winnipeg, Canada
Pintus, Elias; Guy's Hospital, United Kingdom
Sridhar, Srikala S; Princess Margaret Cancer Centre, Canada
Bambury, Richard M; Cork University Hospital, Wilton, Ireland
Emmenegger, Urban; Sunnybrook Health Sciences Centre, Toronto, Canada
Lindberg, Henriette; Herlev University Hospital, Herlev, Denmark
Morris, David; Urology Associates, Nashville
Nolè, Franco; European Institute of Oncology IRCCS, Milan, Italy
Staffurth, John; Velindre University NHS Trust, Cardiff , United Kingdom
Redfern, Charles; Sharp HealthCare, San Diego, CA
Sáez, María I; Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain
Abida, Wassim; Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York
Daugaard, Gedske; Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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