Rucaparib improves radiographic progression-free survival (rPFS) when compared with physician’s choice of therapy in patients with metastatic castration-resistant prostate cancer (mCRPC), according to results from the TRITON3 trial.
Rucaparib improved rPFS in the overall cohort and among patients with BRCA alterations but not among patients with ATM alterations, researchers found.
These findings were presented at the 2023 ASCO Genitourinary Cancers Symposium and published simultaneously in The New England Journal of Medicine.1,2
This phase 3 trial (ClinicalTrials.gov Identifier: NCT02975934) enrolled 405 patients with chemotherapy-naïve mCRPC who had BRCA or ATM alterations.
The patients were randomly assigned to receive 600 mg of rucaparib twice daily (n=270) or physician’s choice of docetaxel (n=75) or a second-generation androgen receptor pathway inhibitor (ARPI; n=60). Baseline characteristics were similar between the treatment arms.
Patients whose disease progressed on physician’s choice of treatment could cross over to the rucaparib arm, and 75% of patients in the physician’s choice arm did so.
In the overall study population, the median rPFS was 10.2 months in the rucaparib arm and 6.4 months in the physician’s choice arm (hazard ratio [HR], 0.61; 95% CI, 0.47-0.80; P =.0003).
Among patients with BRCA alterations, the median rPFS was 11.2 months with rucaparib, 6.4 months with physician’s choice overall (HR, 0.50; 95% CI, 0.36-0.69; P <.0001), 8.3 months with docetaxel (HR, 0.53; 95% CI, 0.37-0.77; P =.0009), and 4.5 months with ARPI (HR, 0.38; 95% CI, 0.25-0.58; P <.0001).
Among patients with ATM alterations, the median rPFS was 8.1 months with rucaparib and 6.8 months with physician’s choice, a nonsignificant difference (HR, 0.95; 95% CI, 0.59-1.52; P =.84).
In the interim overall survival (OS) analysis, there was no significant difference in OS overall or among patients with BRCA alterations.
In the overall cohort, the median OS was 23.6 months with rucaparib and 20.9 months with physician’s choice (HR, 0.94; 95% CI, 0.72-1.23; P =.67). Among patients with BRCA alterations, the median OS was 24.3 months and 20.8 months, respectively (HR, 0.81; 95% CI, 0.58-1.12; P =.21).
All but 1 patient, who was in the second-generation ARPI group, reported at least 1 treatment-emergent adverse event (TEAE). TEAEs led to dose interruptions in 53% of rucaparib recipients, 27% of those who received docetaxel, and 20% of ARPI recipients. Dose reductions occurred in 39%, 30%, and 19%, respectively. Treatment discontinuations occurred in 15%, 32%, and 8%, respectively.
Disclosures: This research was supported by Clovis Oncology, Inc., in collaboration with Foundation Medicine. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Bryce AH, Piulats JM, Reaume MN, et al. Rucaparib for metastatic castration-resistant prostate cancer (mCRPC): TRITON3 interim overall survival and efficacy of rucaparib vs docetaxel or second-generation androgen pathway inhibitor therapy. ASCO GU 2023. February 16-18, 2023. Abstract 18.
2. Fizazi K, Piulats JM, Reaume, MN. Rucaparib or physician’s choice in metastatic prostate cancer. N Engl J Med. Published online February 16, 2023. doi:10.1056/NEJMoa2214676