Here’s a startling fact: Age often complicates treatment decisions in advanced prostate cancer, leaving many patients and doctors unsure of the best path forward. But what if there was a treatment that worked consistently well, regardless of how old you are? New data from the TRITON3 trial suggests that rucaparib (Rubraca) might just be that game-changer for patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). And this is the part most people miss: its benefits actually strengthen with age, offering the greatest risk reduction in patients 75 and older.
Rucaparib, a targeted therapy, has shown remarkable consistency in improving radiographic progression-free survival (rPFS) across all age groups. According to updated findings presented at the 26th Annual Meeting of the Society of Urologic Oncology, patients treated with rucaparib experienced a median rPFS of 11.2 months, compared to just 6.4 months for those on physician’s choice therapy (which included docetaxel or androgen receptor pathway inhibition, or ARPI). But here’s where it gets controversial: While the benefits are clear, some experts wonder if older patients, who often face more side effects, are truly getting the full advantage of this treatment. Should age alone dictate how aggressively we treat mCRPC? Let’s dive deeper.
When the data was broken down by age, the results were striking. Patients under 65 on rucaparib saw a median rPFS of 11.2 months versus 6.3 months with physician’s choice. Those aged 65-74 had similar results: 11.2 months with rucaparib versus 7.6 months with alternative therapy. But the real standout was the 75+ group, where rucaparib delivered a median rPFS of 11.2 months compared to just 5.4 months with physician’s choice. This translated to a 59% reduction in the risk of radiologic progression—a benefit that’s hard to ignore.
Top Takeaways from TRITON3:
1. Consistent Efficacy Across Ages: Rucaparib significantly improved rPFS in all age groups, challenging the notion that older patients respond differently to targeted therapies.
2. Age-Related Risk Reduction: The older the patient, the greater the relative risk reduction in radiologic progression, with the 75+ group seeing the most dramatic benefit.
3. Manageable Safety Profile: While fatigue and anemia were common side effects, no major age-related safety concerns emerged—though anemia rates were higher in older patients.
Alan H. Bryce, MD, and colleagues emphasized in their poster presentation that these findings support rucaparib as a viable treatment option for BRCA-mutated mCRPC, regardless of age. But here’s a thought-provoking question: If rucaparib works so well in older patients, why aren’t more clinicians prescribing it? Could ageism in treatment decisions be holding us back from maximizing patient outcomes?
The TRITON3 study was an open-label, randomized, phase 3 trial that enrolled chemotherapy-naive mCRPC patients with BRCA1/2 or ATM alterations who had previously received second-generation ARPI. Participants were randomized 2:1 to receive either 600 mg of rucaparib twice daily or physician’s choice therapy. The primary endpoint was rPFS, with overall survival (OS) and objective response rate (ORR) as key secondary endpoints.
Earlier data from the trial showed that rucaparib significantly prolonged imaging-based PFS compared to physician’s choice, with a median PFS of 10.2 months versus 6.4 months. In the BRCA-mutated subgroup, median OS with rucaparib was 24.3 months versus 20.8 months with physician’s choice. These results led to the FDA’s accelerated approval of rucaparib in May 2020 for patients with deleterious BRCA mutation–associated mCRPC who had previously received androgen receptor–directed therapy and taxane-based chemotherapy.
Demographics and Baseline Characteristics: Across age groups, most patients were White, with a mix of bone, nodal, and visceral metastases. Prior treatments, including abiraterone acetate, enzalutamide, and docetaxel, were common in both arms. Notably, the majority of patients had received at least one prior therapy for CRPC, highlighting the advanced nature of their disease.
Safety Profile: The most common side effects in the rucaparib arm were fatigue, anemia, nausea, decreased appetite, and diarrhea. While anemia rates increased with age, the overall safety profile remained manageable, with no clear patterns of age-related incidence increases in other side effects.
Final Thoughts: Rucaparib’s consistent efficacy across all age groups—and its particularly strong benefits in older patients—challenges us to rethink how we approach treatment decisions in mCRPC. But here’s the question we leave you with: Are we underutilizing this therapy in older patients due to unfounded concerns about age and side effects? Let us know your thoughts in the comments below.
References:
1. Bryce AH, et al. Efficacy of rucaparib vs physician’s choice in patients with BRCA-mutated mCRPC by age: Results from the TRITON3 study. Society of Urologic Oncology Annual Meeting, 2025.
2. Fizazi K, et al. Rucaparib or physician’s choice in metastatic prostate cancer. N Engl J Med. 2023;388(8):719-732.
3. FDA grants accelerated approval to rucaparib for BRCA-mutated mCRPC. FDA. May 15, 2020.
