The novel combination of talazoparib plus enzalutamide in the first line demonstrated an improvement to imaging-based progression-free survival (PFS) among patients with metastatic castration-resistant prostate cancer, regardless of HRR status, compared with the standard-of-care enzalutamide.

Neeraj Agarwal, MD, Huntsman Cancer Institute at University of Utah, Salt Lake City, UT, presented data from the phase 3 TALAPRO-2 study on Thursday, February 16, 2023, at the 2023 ASCO Genitourinary Cancers Symposium in San Francisco, CA.

This study enrolled 805 patients with metastatic castration-resistant prostate cancer, randomized on a 1-to-1 basis to receive 160 mg enzalutamide plus either 0.5 mg talazoparib (n = 402) or placebo (n = 403). Patients were stratified by prior abiraterone or docetaxel exposure and HRR gene alteration status. The primary end point was imagining-based PFS.

The median imaging-based PFS was not reached in the talazoparib arm, vs 21.9 months in the placebo group. This represented a statistically significant improvement over the standard of care (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.51 to 0.87; P < .001). This improvement was seen across the HRR-deficient, HRR-no-deficient or unknown, and the HRR-non-deficient by tumor tissue testing subgroups. While the overall survival data is currently immature, there is a trend favoring the talazoparib arm (69.4% in the talazoparib arm vs 68% in the placebo arm; HR, 0.89; 95% CI, 0.69 to 1.14; P = .35). Additionally, objective response rates, PSA response by ≥50%, time to PSA progression, and use of subsequent cytotoxic chemotherapy and antineoplastic therapy all significantly favored the talazoparib arm over the placebo arm.

The incidence of grace 3/4 treatment-emergent adverse events was 71.9% in the talazoparib arm and 40.6% in the placebo arm, the most common being anemia, low neutrophil, and low platelet count in the talazoparib arm and hypertension, anemia, and fatigue in the placebo arm. Discontinuation of talazoparib due to treatment-emergent adverse events occurred in 19.1% of patients, compared with 12.2% of placebo. In the talazoparib arm, 10.8% discontinued enzalutamide vs 11.0% in the placebo arm.

Dr Agarwal and coauthors concluded, talazozarib plus enzalutamide  “demonstrated statistically significant and clinically meaningful improvement in [imaging-based] PFS over standard of care [enzalutamide] as [first-line] treatment in patients with [metastatic castration-resistant prostate cancer] regardless of HRR status, while delaying time to worsening in [global health status/quality of life].”

Source:

Agarwal N, Azad A, Carles J, et al. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract LBA17