Rucaparib or physician's choice in metastatic prostate cancer

Fizazi, Karim, Piulats, Josep M., Reaume, M. Neil, Ostler, Peter, McDermott, Ray, Gingerich, Joel R., Pintus, Elias, Sridhar, Srikala S., Bambury, Richard M., Emmenegger, Urban, Lindberg, Henriette, Morris, David, Nolè, Franco, Staffurth, John ORCID: https://orcid.org/0000-0002-7834-3172, Redfern, Charles, Sáez, María I., Abida, Wassim, Daugaard, Gedske, Heidenreich, Axel, Krieger, Laurence, Sautois, Brieuc, Loehr, Andrea, Despain, Darrin, Heyes, Catherine A., Watkins, Simon P., Chowdhury, Simon, Ryan, Charles J. and Bryce, Alan H. 2023. Rucaparib or physician's choice in metastatic prostate cancer. New England Journal of Medicine 388 (8) , pp. 719-732. 10.1056/NEJMoa2214676

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Abstract

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. opens in new tab.)

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Massachusetts Medical Society
ISSN:	0028-4793
Date of First Compliant Deposit:	17 March 2023
Date of Acceptance:	16 February 2023
Last Modified:	16 Aug 2023 16:20
URI:	https://orca.cardiff.ac.uk/id/eprint/157781

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