Dr Vaishampayan on the Use of Talazoparib and Enzalutamide in Patients With HRR Gene–Mutated mCRPC

Ulka Nitin Vaishampayan, MBBS, director, the Phase I Program, Rogel Cancer Center, professor, internal medicine, University of Michigan, discusses the need for improved identification of patients with homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC) who may benefit from treatment with talazoparib (Talzenna) and enzalutamide (Xtandi).

On June 20, 2023, the FDA approved talazoparib plus enzalutamide for patients with HRR gene–mutated mCRPC based on findings from the phase 3 TALAPRO-2 trial (NCT03395197). Notably, the double-blind, placebo-controlled, multicohort trial included patients previously treated with docetaxel in the metastatic hormone-sensitive setting, although they made up a small proportion of the study population, Vaishampayan says. Patients were also required to have progressed on prior androgen deprivation therapy (ADT), she adds.

Results showed that radiographic progression-free survival (rPFS) significantly improved with talazoparib and enzalutamide vs enzalutamide alone in this population, Vaishampayan reports. Median rPFS was not yet reached in the experimental arm, and was 13.8 months in the control arm.

Ideal candidates for this regimen may include patients without prior exposure to an androgen receptor (AR) inhibitor, Vaishampayan continues. However, the use of AR inhibitors in intensified therapeutic regimens has become a standard approach for patients with metastatic hormone-sensitive prostate cancer, Vaishampayan states. Moreover, there is a lack of evidence supporting the regimen's use in patients with mCRPC who already received abiraterone acetate (Zytiga), enzalutamide, or apalutamide (Erleada), or a triplet regimen consisting of ADT plus darolutamide and docetaxel, she notes. Accordingly, it can be difficult to justify administering talazoparib plus enzalutamide to this AR inhibitor–naive population, Vaishampayan says.

These data also suggest that talazoparib plus enzalutamide may provide benefit to patients who experienced disease progression with prostate-specific antigen relapse after treatment with ADT, and now have mCRPC, Vaishampayan adds. Patients in this population who harbor HRR mutations, should be considered for this regimen, Vaishampayan concludes.