Rucaparib or Physician's Choice in Metastatic Prostate Cancer
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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; 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; Bryce, Alan H; TRITON3 Investigators.
In: NEW ENGL J MED, Vol. 388, No. 8, 23.02.2023, p. 719-732.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -