Dr Agarwal on the FDA Approval of Talazoparib Plus Enzalutamide in HRR-Mutated mCRPC

Neeraj Agarwal, MD, professor, medicine, Presidential Endowed Chair, Cancer Research, director, Genitourinary Oncology Program, director, Center of Investigational Therapeutics, Huntsman Cancer Institute, University of Utah, discusses the significance of the FDA approval of talazoparib (Talzenna) plus enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations.

On June 20, 2023, the FDA approved the combination of talazoparib and enzalutamide in patients with HRR gene–mutated mCRPC. This regulatory decision was supported by findings from the phase 3 TALAPRO-2 trial (NCT03395197), in which 399 patients with mCRPC with HRR gene mutations were randomly assigned to receive either talazoparib plus enzalutamide or enzalutamide plus placebo. In this trial, the median radiographic progression-free survival (rPFS) with the combination in the HRR-mutated population was not yet reached compared with 13.8 months with enzalutamide alone. The hazard ratio for rPFS was 0.45 (95% CI, 0.33-0.61), translating to a 55% reduction in the risk of progression or death with the combination vs the monotherapy.

In addition, although the overall survival (OS) data from this trial are not yet mature, they indicate a strong trend toward a survival benefit with the combination compared with enzalutamide alone, Agarwal says. Beyond rPFS and OS, positive outcomes were seen with other end points that are important to patients, such as the time to subsequent chemotherapy, Agarwal emphasizes. The time to prostate-specific antigen progression was favorable with the combination vs with enzalutamide alone, according to Agarwal.

Time to deterioration of quality of life (QOL) was measured in TALAPRO-2 using standardized questionnaires that have been validated and used in several clinical trials around the world, Agarwal notes. Those who received the combination experienced a delay in deterioration of QOL compared with enzalutamide alone, Agarwal explains. As QOL data provide a sum of the efficacy and toxicity profiles of treatment regimens, the maintained QOL outcomes with talazoparib plus enzalutamide further support the use of this combination in patients with HRR-mutated mCRPC, Agarwal concludes.