Rucaparib or Physician's Choice in Metastatic Prostate Cancer

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) with deleterious BRCA alterations presents a therapeutic challenge.
• Previous phase 2 studies indicated activity of rucaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in this setting.
• Further data were required to validate these preliminary findings.

Purpose of the Study:

• To evaluate the efficacy of rucaparib compared to standard treatments in patients with mCRPC harboring BRCA1, BRCA2, or ATM alterations.
• To assess the impact of rucaparib on imaging-based progression-free survival in this specific patient group.

Main Methods:

• A randomized, controlled, phase 3 trial (TRITON3) was conducted.
• Patients with mCRPC and a documented BRCA1, BRCA2, or ATM alteration, who progressed after second-generation androgen-receptor pathway inhibitor (ARPI) treatment, were enrolled.
• Participants were randomized 2:1 to receive oral rucaparib (600 mg twice daily) or physician's choice of docetaxel or a second-generation ARPI.

Main Results:

• The study included 270 patients receiving rucaparib and 135 in the control arm (intention-to-treat).
• In the BRCA-altered subgroup, median imaging-based progression-free survival was 11.2 months with rucaparib versus 6.4 months with control (HR, 0.50; 95% CI, 0.36 to 0.69).
• Rucaparib demonstrated a significant improvement in progression-free survival in both the BRCA subgroup and the overall intention-to-treat population.

Conclusions:

• Rucaparib significantly prolonged imaging-based progression-free survival compared to control medication in patients with mCRPC and BRCA alterations.
• Rucaparib represents a promising therapeutic option for patients with mCRPC and specific genetic alterations.
• Fatigue and nausea were the most common adverse events associated with rucaparib treatment.