Opinion
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Neeraj Agarwal, MD, on talazoparib/enzalutamide efficacy by HRR gene mutation status
Author(s):
"We see the overall survival, whether it is [in] all-comers, in HRR gene mutation-positive patients, or in HRR gene [mutation]-negative patients or [those] who did not have mutations, the overall survival is about 45 to 47 months," says Neeraj Agarwal, MD, FACS.
Data from the phase 3 TALAPRO-2 trial (NCT03395197) showed that the combination of enzalutamide (Xtandi) plus talazoparib (Talzenna) led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC).1 These data were recently presented at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.
In a recent interview with Urology Times®, Neeraj Agarwal, MD, FACS, shares the OS results in patients stratified by HRR gene mutation status. Overall, both HRR mutation-negative and HRR mutation-positive patients demonstrated an improvement in OS with the combination vs enzalutamide alone, though the benefit was more pronounced in those who had HRR mutations.
Agarwal is professor of medicine and the director of the genitourinary oncology program at the Huntsman Cancer Institute of the University of Utah in Salt Lake City.
In the subgroup analysis, the addition to talazoparib improved OS in patients who were HRR-deficient (n = 169; HR, 0.549; 95% CI, 0.364–0.826; P = .0035) and in patients who were HRR–non-deficient/unknown (n = 636; HR, 0.878; 95% CI, 0.713–1.080; P = .218).
According to Agarwal, in the patients who did the not have HRR mutations, the OS was 46.6 months in the combination arm vs 37.4 months in the enzalutamide alone arm. Among those who did have HRR mutations, the OS was 45 months in the combination arm vs 31 months in the enzalutamide alone arm.
Agarwal concluded, “These are all meaningful improvement in survival, although survival advantage is more in patients who had HRR gene mutations. That’s why we should continue to obtain comprehensive genomic profiling or NGS testing for all patients with metastatic prostate cancer.”
REFERENCE
1. Agarwal N, Azad A, Carles J, et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. J Clin Oncol. 43, 2025 (suppl 5; abstr LBA18). doi:10.1200/JCO.2025.43.5_suppl.LBA18
