Treating Metastatic Prostate Cancer: Rucaparib or Physician’s Choice?

At the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium, Alan Bryce, MD, presented new results from phase 3 of the TRITON study (TRITON3) on rucaparib versus physician’s choice of treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The phase 2 study showed that rucaparib has a high level of activity in patients with mCRPC.

The TRITON3 study enrolled 4855 patients with mCRPC who had a BRCA1, BRCA2, or ataxia-telangiectasia mutated (ATM) alteration. Patients had experienced disease progression after receiving treatment with a second-generation androgen receptor pathway inhibitor (ARPI).

Patients were assigned in a 2:1 ratio to receive either oral rucaparib 600 mg twice daily or a physician’s choice control—either docetaxel or a different second-generation ARPI, including abiraterone acetate or enzalutamide. The primary outcome was median duration of imaging-based progression-free survival (PFS) according to an independent review.

Of the 4855 patients enrolled in the study, 270 patients were given rucaparib, and 135 received a control medication (intention-to-treat group). In both groups, 201 patients and 101 patients, respectively, had a BRCA alteration.

The rucaparib group demonstrated a significantly longer duration of imaging-based PFS compared with the control group at 62 months, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio [HR], 0.50; 95% CI, 0.36-0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; HR, 0.61; 95% CI, 0.47-0.80; P<.001 for both comparisons).

An exploratory analysis conducted in the ATM alteration subgroup showed that the median duration of imaging-based PFS was 8.1 months in the rucaparib group and 6.8 months in the control group (HR, 0.95; 95% CI, 0.59-1.52). The most frequent adverse events were fatigue and nausea.

Results of the TRITON3 study demonstrated that patients with mCRPC and a BRCA alteration had a significantly longer duration of imaging-based PFS when treated with rucaparib as opposed to a control medication.