TY - JOUR
T1 - Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration
T2 - Final Results from the Phase 2 TRITON2 Study
AU - Abida, Wassim
AU - Campbell, David
AU - Patnaik, Akash
AU - Bryce, Alan H
AU - Shapiro, Jeremy
AU - Bambury, Richard M
AU - Zhang, Jingsong
AU - Burke, John M
AU - Castellano, Daniel
AU - Font, Albert
AU - Ganju, Vinod
AU - Hardy-Bessard, Anne-Claire
AU - McDermott, Ray
AU - Sautois, Brieuc
AU - Spaeth, Dominique
AU - Voog, Eric
AU - Piulats, Josep M
AU - Pintus, Elias
AU - Ryan, Charles J
AU - Merseburger, Axel S
AU - Daugaard, Gedske
AU - Heidenreich, Axel
AU - Fizazi, Karim
AU - Loehr, Andrea
AU - Despain, Darrin
AU - Simmons, Andrew D
AU - Dowson, Melanie
AU - Go, Jowell
AU - Watkins, Simon P
AU - Chowdhury, Simon
N1 - Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.
PY - 2023/9
Y1 - 2023/9
N2 - BACKGROUND: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration.OBJECTIVE: To present the final data from TRITON2.DESIGN, SETTING, AND PARTICIPANTS: TRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR; as per the modified Response Evaluation Criteria in Solid Tumor Version 1.1/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease by independent radiology review [IRR]); prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) was a key secondary endpoint.RESULTS AND LIMITATIONS: As of July 27, 2021 (study closure), TRITON2 had enrolled 277 patients, grouped by mutated gene: BRCA (n = 172), ATM (n = 59), CDK12 (n = 15), CHEK2 (n = 7), PALB2 (n = 11), or other DDR gene (Other; n = 13). ORR by IRR was 46% (37/81) in the BRCA subgroup (95% confidence interval [CI], 35-57%), 100% (4/4) in the PALB2 subgroup (95% CI, 40-100%), and 25% (3/12) in the Other subgroup (95% CI, 5.5-57%). No patients within the ATM, CDK12, or CHEK2 subgroups had an objective response by IRR. PSA50 response rates (95% CI) in the BRCA, PALB2, ATM, CDK12, CHEK2, and Other subgroups were 53% (46-61%), 55% (23-83%), 3.4% (0.4-12), 6.7% (0.2-32%), 14% (0.4-58%), and 23% (5.0-54%), respectively.CONCLUSIONS: The final TRITON2 results confirm the clinical benefit and manageable safety profile of rucaparib in patients with mCRPC, including those with an alteration in BRCA or select non-BRCA DDR gene.PATIENT SUMMARY: Almost half of TRITON2 patients with BRCA-mutated metastatic castration-resistant prostate cancer had a complete or partial tumor size reduction with rucaparib; clinical benefits were also observed with other DNA damage repair gene alterations.
AB - BACKGROUND: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration.OBJECTIVE: To present the final data from TRITON2.DESIGN, SETTING, AND PARTICIPANTS: TRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR; as per the modified Response Evaluation Criteria in Solid Tumor Version 1.1/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease by independent radiology review [IRR]); prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) was a key secondary endpoint.RESULTS AND LIMITATIONS: As of July 27, 2021 (study closure), TRITON2 had enrolled 277 patients, grouped by mutated gene: BRCA (n = 172), ATM (n = 59), CDK12 (n = 15), CHEK2 (n = 7), PALB2 (n = 11), or other DDR gene (Other; n = 13). ORR by IRR was 46% (37/81) in the BRCA subgroup (95% confidence interval [CI], 35-57%), 100% (4/4) in the PALB2 subgroup (95% CI, 40-100%), and 25% (3/12) in the Other subgroup (95% CI, 5.5-57%). No patients within the ATM, CDK12, or CHEK2 subgroups had an objective response by IRR. PSA50 response rates (95% CI) in the BRCA, PALB2, ATM, CDK12, CHEK2, and Other subgroups were 53% (46-61%), 55% (23-83%), 3.4% (0.4-12), 6.7% (0.2-32%), 14% (0.4-58%), and 23% (5.0-54%), respectively.CONCLUSIONS: The final TRITON2 results confirm the clinical benefit and manageable safety profile of rucaparib in patients with mCRPC, including those with an alteration in BRCA or select non-BRCA DDR gene.PATIENT SUMMARY: Almost half of TRITON2 patients with BRCA-mutated metastatic castration-resistant prostate cancer had a complete or partial tumor size reduction with rucaparib; clinical benefits were also observed with other DNA damage repair gene alterations.
KW - DNA Damage
KW - Genes, BRCA2
KW - Humans
KW - Indoles/therapeutic use
KW - Male
KW - Prostatic Neoplasms, Castration-Resistant/drug therapy
KW - Metastatic castration-resistant prostate cancer
KW - Poly(ADP-ribose) polymerase inhibitor
KW - DNA damage repair gene alteration
UR - http://www.scopus.com/inward/record.url?scp=85163365508&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2023.05.021
DO - 10.1016/j.eururo.2023.05.021
M3 - Journal article
C2 - 37277275
SN - 0302-2838
VL - 84
SP - 321
EP - 330
JO - European Urology
JF - European Urology
IS - 3
ER -