Rucaparib or Physician's Choice in Metastatic Prostate Cancer

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 KriegerBrieuc Sautois, Andrea Loehr, Darrin Despain, Catherine A. Heyes, Simon P. Watkins, Simon Chowdhury, Charles J. Ryan, Alan H. Bryce

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)719-732
Number of pages14
JournalNew England Journal of Medicine
Volume388
Issue number8
DOIs
StatePublished - 2023

Bibliographical note

Funding Information:
Supported by Clovis Oncology . Dr. Abida’s work is supported by a grant (P30-CA008748) from the National Cancer Institute .

Publisher Copyright:
© 2023 Massachusetts Medical Society.

Keywords

  • Cancer
  • Genetics
  • Genitourinary Cancer
  • Hematology/Oncology
  • Treatments in Oncology
  • Urology/Prostate Disease
  • Urology/Prostate Disease General

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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