Dr Agarwal on Future Questions to Address Following the TALAPRO-2 Trial in 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 future questions to be addressed following the phase 3 TALAPRO-2 trial (NCT03395197) evaluating the combination of talazoparib (Talzenna) plus enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC).

The phase 3 study met its primary end point, with the combination eliciting a statistically significant and clinically meaningful improvement in progression-free survival compared with enzalutamide plus placebo in patients with previously untreated mCRPC, irrespective of homologous recombination repair (HRR) gene–mutation status. However, when the FDA approved talazoparib plus enzalutamide in June 2023, it was only indicated for patients with HRR gene–mutated mCRPC, Agarwal begins. Although the non–HRR gene–mutated population also derived a PFS benefit, the combination is not indicated for use in this group of patients.

Clinicians are still seeking to better understand which patients are deriving the most benefit and what is driving those responses, Agarwal expands. If investigators are able to pinpoint why exactly patients with HRR mutations are benefiting, this will allow more patients to benefit from the combination in the future, he says. Investigators will also want to better understand the pathway of resistance and the molecular pathways, he adds.

Another area of concern in following the TALAPRO-2 trial is how to best contain toxicity, Aggarwal continues. Notably, it was found that the quality of life (QOL) and the time to deterioration of QOL was better with the combination of enzalutamide and talazoparib compared with enzalutamide alone. However, a better real-world understanding is still needed to help improve QOL for patients receiving this regimen, making it important to understand when dose reductions or pauses may be necessary, he emphasizes. Ultimately, the data from this trial led to the approval of a new combination to treat patients with mCRPC, and real-world use will continue to build upon these findings, Agarwal concludes.