The data, which were shared during the 26th Annual Meeting of the Society of Urologic Oncology, showed that in the overall BRCA-mutated population, rucaparib (n = 201) continued to provide a meaningful rPFS advantage over physician’s choice of therapy (n = 101), at a median of 11.2 months and 6.4 months, respectively (HR, 0.50; 95% CI, 0.36-0.69).
When broken down by age, those under 65 years who received rucaparib experienced a median rPFS of 11.2 months (95% CI, 8.7-14.2) vs 6.3 months (95% CI, 2.3-12.0) with physician’s choice of therapy (HR, 0.60; 95% CI, 0.33-1.08). Those between the ages of 65 and 74 years experienced a median rPFS of 11.2 months (95% CI, 8.2-16.5) with rucaparib vs 7.6 months (95% CI, 5.7-9.0) with physician’s choice of therapy (HR, 0.46; 95% CI, 0.28-0.75). Notably, in those aged 75 years or older, the median rPFS in the respective arms was 11.2 months (95% CI, 8.3-15.0) and 5.4 months (95% CI, 3.7-8.4), respectively (HR, 0.41; 95% CI, 0.22-0.74); this translated to a 59% reduction in the risk of radiologic progression.
“These findings support the use of rucaparib as a treatment option in patients with BRCA-mutated mCRPC independent of age,” Alan H. Bryce, MD, a medical oncologist and interim president and chief clinical officer of City of Hope Cancer Center,Phoenix, in Arizona, and colleagues, wrote in a poster.
What was the design of the TRITON3 study examining rucaparib in mCRPC?
The open-label, randomized, phase 3 trial enrolled patients with chemotherapy-naive mCRPC harboring BRCA1/2 or ATM alterations who had previously received a second-generation ARPI in any setting. Participants were randomized 2:1 to receive 600 mg of rucaparib twice daily (n = 270) or physician’s choice of therapy (n = 135), which could have been docetaxel (n = 75) or a second-generation ARPI like abiraterone acetate (Zytiga) or enzalutamide (Xtandi; n = 60).
Patients were stratified based on ECOG performance status (0 vs 1), the presence of liver metastases (yes vs no), and mutational profile (BRCA1 vs BRCA2 vs ATM). Treatment continued until disease progression; after that, treatment was stopped, patients crossed over to receive rucaparib per physician judgment, or they received treatment beyond progression with patient consent.
The primary end point was rPFS by blinded independent central review (BICR), and key secondary end points included overall survival (OS) and objective response rate (ORR) by BICR.
Primary data from the study showed that at 62 months, rucaparib significantly prolonged imaging-based PFS vs physician’s choice.2 In the intention-to-treat population, the median duration of imaging-based PFS was 10.2 months (95% CI, 8.3-11.2) with rucaparib vs 6.4 months (95% CI, 5.6-8.2) with physician’s choice of therapy (HR, 0.61; 95% CI, 0.47-0.80; P < .001). In the subgroup of patients with ATM mutations, the median duration of imaging-based PFS with the respective approaches was 8.1 months (95% CI, 5.5-8.3) and 6.8 months (95% CI, 4.0-10.4; HR, 0.95; 95% CI, 0.59-1.52). Moreover, in the BRCA-mutated subgroup, the median OS with rucaparib was 24.3 months (95% CI, 19.9-25.7) vs 20.8 months (95% CI, 16.3-23.1) with physician’s choice of therapy (HR, 0.81; 95% CI, 0.58-1.12; P = .21).
In May 2020, the FDA granted accelerated approval to rucaparib (Rubraca) for use in patients with deleterious BRCA mutation–associated mCRPC who previously received androgen receptor–directed therapy and a taxane-based chemotherapy.3 The decision was supported by findings from the phase 2 TRITON2 trial (NCT02952534), in which rucaparib elicited a confirmed ORR of 44% (95% CI, 31%-57%) with a median duration of response that was not evaluable (NE; 95% CI, 6.4-NE).
Subgroup analyses from the trial focused on OS and rPFS with rucaparib vs physician’s choice of therapy.2 The analysis shared during the meeting sought to evaluate the link between age and clinical benefit achieved with rucaparib.1
What were the demographics and baseline disease characteristics by age group?
In those under 65 years (n = 97), the median patient age was 59 years (range, 45-64) in the rucaparib arm (n = 97) and 61 years (range, 47-64) in the physician’s choice arm (n = 29). More than half of patients were White (59% vs 62%). Regarding an ECOG performance status, 50% vs 55% had a status of 0, and 50% vs 45% had a status of 1. In the rucaparib arm, 87% had distant bone metastases, 44% had nodal metastases, and 31% had visceral metastases; in the physician’s choice, the respective rates were 93%, 35%, and 28%. In the rucaparib arm, 57% had prior abiraterone acetate, 47% had prior enzalutamide, and 38% had prior docetaxel for hormone-sensitive disease; in the physician’s choice, these rates were 59%, 45%, and 38%, respectively. Most patients in the respective arms received 1 or more therapies for cRPC (84% vs 69%).
In those with 65 and 74 years (n = 117), the median patient age was 70 years (range, 65-74) in the rucaparib arm (n = 76) vs 69 years (range, 65-74) in the physician’s choice arm (n = 41). Most patients were White (80% vs 88%). In the rucaparib arm, 46% had an ECOG performance status of 0 and 54% had a status of 1; in the physician’s choice arm, these rates were 63% and 37%. Patients had distant bone (88% vs 78%), nodal (46% vs 44%), and visceral (28% vs 27%) metastases. In the rucaparib arm, patients previously received abiraterone acetate (57%), enzalutamide (41%), and docetaxel (25%); in the physician’s choice arm, these respective arms were 63%, 44%, and 12%. The majority of patients in this group also previously received at least 1 therapy for CRPC (82% vs 88%).
In those at least 75 years (n = 88), the median patient age in the rucaparib arm (n = 57) was 79 years (range, 75-90) vs 78 years (range, 75-92) in the physician’s choice arm (n = 31). Most patients were White (79% vs 87%) and had an ECOG performance status of 1 (51% vs 74%). In the rucaparib arm, most patients had bone metastases (83%), nodal metastases (44%), and visceral metastases (33%); these rates were 84%, 58%, and 52%, respectively, in the physician’s choice arm. Moreover, those in the rucaparib arm previously received abiraterone acetate (53%), enzalutamide (44%), and docetaxel (11%); these respective rates were 61%, 45%, and 10%. Moreover, 75% and 71% of patients received at least 1 prior therapy for CRPC.
What was the safety profile of rucaparib in this population?
The most common treatment-emergent adverse effects (TEAEs) in the rucaparib arm were asthenia/fatigue (range, 55%-67%), anemia/hemoglobin decreased (range, 31%-65%), nausea (49%-55%), decreased appetite (range, 32%-53%), and diarrhea (range, 21%-38%).
“The incidence of anemia increased with age in both the rucaparib and physician’s choice arms, and the incidence of decreased appetite increased with older age in the rucaparib arm. There were no clear patterns of age-related incidence increases in the other most common TEAEs,” the study authors wrote. “The incidence of grade 3 or higher asthenia/fatigue and anemia was highest in the oldest age group in the rucaparib arm.”
References
- Bryce AH, Piulats JP, Ryan CJ, et al. Efficacy of rucaparib vs physician’s choice in patients with BRCA-mutated metastatic castration-resistant prostate cancer by age: Results from the TRITON3 study. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Poster #176.
- Fizazi K, Piulats JM, Reaume MN, et al. Rucaparib or physician’s choice in metastatic prostate cancer. N Engl J Med. 2023;388(8):719-732. doi:10.1056/NEJMoa2214676
- FDA grants accelerated approval to rucaparib for BRCA-mutated metastatic castration-resistant prostate cancer. FDA. May 15, 2020. Accessed December 5, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate
