Rucaparib or Physician's Choice in Metastatic Prostate Cancer

TY - JOUR

T1 - Rucaparib or Physician's Choice in Metastatic Prostate Cancer

AU - Fizazi, Karim

AU - Piulats, Josep M

AU - Reaume, M Neil

AU - Ostler, Peter

AU - McDermott, Ray

AU - Gingerich, Joel R

AU - Pintus, Elias

AU - Sridhar, Srikala S

AU - Bambury, Richard M

AU - Emmenegger, Urban

AU - Lindberg, Henriette

AU - Morris, David

AU - Nolè, Franco

AU - Staffurth, John

AU - Redfern, Charles

AU - Sáez, María I

AU - Abida, Wassim

AU - Daugaard, Gedske

AU - Heidenreich, Axel

AU - Krieger, Laurence

AU - Sautois, Brieuc

AU - Loehr, Andrea

AU - Despain, Darrin

AU - Heyes, Catherine A

AU - Watkins, Simon P

AU - Chowdhury, Simon

AU - Ryan, Charles J

AU - Bryce, Alan H

AU - TRITON3 Investigators

AU - Steuber, Thomas

N1 - Copyright © 2023 Massachusetts Medical Society.

PY - 2023/2/23

Y1 - 2023/2/23

N2 - 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.).

AB - 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.).

KW - Humans

KW - Male

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Indoles/therapeutic use

KW - Progression-Free Survival

KW - Prostatic Neoplasms, Castration-Resistant/drug therapy

KW - Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use

KW - Androgen Antagonists/therapeutic use

KW - Antineoplastic Agents/therapeutic use

KW - Docetaxel/therapeutic use

KW - Disease Progression

KW - Genes, BRCA1

KW - Genes, BRCA2

U2 - 10.1056/NEJMoa2214676

DO - 10.1056/NEJMoa2214676

M3 - SCORING: Journal article

C2 - 36795891

VL - 388

SP - 719

EP - 732

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 8

ER -