Rucaparib for the treatment of metastatic castration-resistant prostate cancer associated with a DNA damage repair gene alteration: Final results from the phase 2 TRITON2 study Journal Article
| Authors: | Abida, W.; Campbell, D.; Patnaik, A.; Bryce, A. H.; Shapiro, J.; Bambury, R. M.; Zhang, J.; Burke, J. M.; Castellano, D.; Font, A.; Ganju, V.; Hardy-Bessard, A. C.; McDermott, R.; Sautois, B.; Spaeth, D.; Voog, E.; Piulats, J. M.; Pintus, E.; Ryan, C. J.; Merseburger, A. S.; Daugaard, G.; Heidenreich, A.; Fizazi, K.; Loehr, A.; Despain, D.; Simmons, A. D.; Dowson, M.; Go, J.; Watkins, S. P.; Chowdhury, S. |
| Article Title: | Rucaparib for the treatment of metastatic castration-resistant prostate cancer associated with a DNA damage repair gene alteration: Final results from the phase 2 TRITON2 study |
| Abstract: | 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. © 2023 |
| Keywords: | adult; controlled study; treatment response; gene mutation; major clinical study; overall survival; constipation; fatigue; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; cancer patient; outcome assessment; prostate specific antigen; dna repair; disease association; progression free survival; phase 2 clinical trial; anemia; nausea; thrombocytopenia; vomiting; hemoglobin; brca1 protein; brca2 protein; asthenia; rash; tumor suppressor gene; alanine aminotransferase; aspartate aminotransferase; atm protein; open study; checkpoint kinase 2; platelet count; adult respiratory distress syndrome; decreased appetite; response evaluation criteria in solid tumors; rucaparib; metastatic castration-resistant prostate cancer; human; male; article; metastatic castration resistant prostate cancer; poly(adp-ribose) polymerase inhibitor; partner and localizer of brca2; dna damage repair gene alteration; torsade de pointes |
| Journal Title: | European Urology |
| Volume: | 84 |
| Issue: | 3 |
| ISSN: | 0302-2838 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2023-09-01 |
| Start Page: | 321 |
| End Page: | 330 |
| Language: | English |
| DOI: | 10.1016/j.eururo.2023.05.021 |
| PUBMED: | 37277275 |
| PROVIDER: | scopus |
| PMCID: | PMC10527050 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: W. Abida -- Source: Scopus |
