Dr. Zhang on Key Phase 3 Trials for PARP Inhibitors in mCRPC

Tian Zhang, MD, MHS, associate professor, the Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses key phase 3 trials evaluating PARP inhibitors in the treatment of metastatic castration-resistance prostate cancer (mCRPC).

The phase 3 trials that have examined PARP inhibitor monotherapy include the PROfound trial (NCT02987543), which evaluated olaparib (Lynparza) compared with abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with mCRPC who have failed prior treatment with a new hormonal agent and have homologous recombination repair (HRR) gene mutations, Zhang begins. The TRITON3 trial (NCT02975934) also tested rucaparib (Rubraca) against standard of care in patients with mCRPC with homologous recombination deficiency.

Findings from the PROfound trial were positive, showing that olaparib prolonged radiographic progression-free survival (rPFS). Data from the study supported the FDA approval of olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR gene–mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone acetate.

Findings from TRITON3 presented at the 2023 Genitourinary Cancers Symposium showed that rucaparib generated an improvement in median rPFS compared with physician’s choice of therapy for men with BRCA-altered mCRPC.

Looking specifically at patients in the control arm of TRITON3 who received docetaxel vs those who received an androgen receptor (AR)–targeted agent, the rPFS benefit for rucaparib was slightly less over docetaxel compared with the rPFS benefit observed vs an AR-targeted agent, Zhang notes. In the intent-to-treat population, rucaparib was more effective in the population with HRR defects, Zhang concludes.