(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA was host to a prostate cancer poster session. Dr. Alan Bryce presented the final overall survival and safety data from TRITON3, a phase III trial of rucaparib versus docetaxel or 2nd generation androgen receptor pathway inhibitor (ARPI) for metastatic castration-resistant prostate cancer (mCRPC).
TRITON3 (NCT02975934) is an open-label, randomized, phase III trial of rucaparib, a PARP inhibitor, versus physician's choice of therapy, in men with chemotherapy-naïve mCRPC and BRCA1 or BRCA2 (BRCA1/2) or ATM gene alterations. The control arm of physician's choice of therapy included docetaxel or a second-generation ARPI, abiraterone acetate or enzalutamide.
The primary results from the TRITON3 study demonstrated that rucaparib significantly improved radiographic progression-free survival, the primary efficacy endpoint, versus physician's choice.1 Here, Dr. Bryce and colleagues reported the final overall survival and safety results from TRITON3.
Men ≥18 years of age with histologically or cytologically confirmed mCRPC and a BRCA1/2 or ATM alteration were eligible for enrollment. Patients had a history of disease progression following treatment with one previous second-generation ARPI. Eligible patients were randomized 2:1 to rucaparib 600 mg twice daily or physician's choice of therapy.
During randomization, investigators chose the next choice of therapy (docetaxel, abiraterone acetate, or enzalutamide) for each patient before randomization to the rucaparib or physician’s choice arms. OS was a key secondary endpoint tested initially in the BRCA subgroup, followed by the intent-to-treat (ITT) population in an ordered step-down multiple-comparisons procedure. Crossover from physician’s choice to rucaparib was allowed after radiographic progression was confirmed by independent radiology review.
Dr. Bryce noted that patient demographics and baseline characteristics have been reported previously. Rucaparib significantly improved rPFS, the primary endpoint of TRITON3 versus physician's choice of therapy (hazard ratio [HR], 0.50 [95% CI, 0.36-0.69]).
Of the 135 patients in the physician's choice arm of the ITT population, 94 were eligible to cross over to rucaparib. Of these, 70 (74.5%) crossed over.
At a median follow-up of 44 months, the median OS in the BRCA subgroup in the rucaparib arm was 23.2 versus 21.2 months for the physician’s choice control arm (HR, 0.91 [95% CI, 0.68-1.20]; p= 0.5044).
The figure below presents OS data for patients randomized to rucaparib who would have received docetaxel if randomized to the physician's choice arm versus those who received docetaxel (left), and patients randomized to rucaparib who would have received an ARPI if randomized to the physician's choice arm versus those who received an ARPI (right). Hierarchical testing did not continue owing to a lack of statistical significance.
OS was similar in rucaparib versus physician's choice arms in the ITT population (HR, 0.99 [95% CI, 0.78-1.26]) and ATM (HR, 1.21 [95% CI, 0.77-1.901) subgroup. The HR of the OS was similar for both the BRCA1 and BRCA2 subpopulations and the overall BRCA population; however, the median OS for those with BRCA1 mutations was 12.1 months for rucaparib versus 11.8 months for physician's choice, and for those with BRCA2 mutations, median OS was 24.0 versus 22.0 months, respectively.
The median duration of treatment in the rucaparib and physician’s choice arms was 8.3 and 5.1 months, respectively. With rucaparib, the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) and TEAEs leading to dose reductions and interruptions was higher, while discontinuations due to TEAEs were lower than with physician's choice.
The most frequent any-grade TEAE in the rucaparib (n = 270) and physician's choice (n = 130) arms was asthenia/fatigue (61.5% and 63.1%, respectively). The most frequent grade ≥3 TEAE was anemia (23.7%) with rucaparib and asthenia/fatigue (9.2%) with physician's choice.
Dr. Bryce concluded as follows:
- Rucaparib remains the only PARP inhibitor to show an improved radiographic progression-free survival (rPFS) versus a docetaxel-containing control arm
- Overall survival (OS) was similar in both arms even when most patients in the physician's choice arm crossed over to rucaparib
- No new safety signals were observed.
- These data support rucaparib as a treatment option for patients with BRCA-mutated mCRPC.
Presented by: Alan Bryce, MD, Professor of Molecular Medicine at Translational Genomics Research Institute, Chief Clinical Officer, City of Hope, Phoenix, AZ
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
Related content: TRITON3 Final Overall Survival Results for Rucaparib in BRCA-Mutated Prostate Cancer - Alan Bryce
References:
- Fizazi K, Piulats JM, Reaume MN, et al. Rucaparib or Physician’s Choice in Metastatic Prostate Cancer. N Engl J Med. 2023; 388(8):719-32.