Dr. Abida on the Limitations of PARP Inhibitors in Prostate Cancer

Wassim Abida, MD, PhD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the limitations of PARP inhibitors in prostate cancer.

Rucaparib (Rubraca) was granted accelerated approval by the FDA for use in men with deleterious, germline or somatic BRCA mutation–associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with an androgen receptor–directed therapy and a taxane-based chemotherapy. However, findings from the pivotal, phase 2 TRITON2 trial (NCT02952534) demonstrated that patients with BRCA2 mutations derived higher prostate-specific antigen responses with rucaparib compared with patients with BRCA1 mutations, Abida says.

Olaparib (Lynparza) is FDA approved for use in men with deleterious or suspected deleterious germline or somatic homologous recombination repair gene–mutated mCRPC who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga). The pivotal, phase 3 PROfound trial (NCT02987543) enrolled patients with mCRPC who harbored BRCA1/2 or ATM mutations in 1 cohort and patients who harbored mutations in 12 other prespecified genes in another cohort. The results revealed that not all mutated genes yielded similar sensitivity to olaparib; however, the FDA approval does not specify which patients are more likely to respond to the PARP inhibitor, Abida explains.

As such, when selecting treatment with a PARP inhibitor for a patient with mCRPC, it is critical to understand their likelihood of response based on specific genetic markers, Abida says. Additional research is needed to understand how to better target tumors that harbor mutations associated with lower response rates, concludes Abida.