Phase 3 TALAPRO-3 Supports Early Use of Talazoparib in HRR-Mutated mCS Prostate Cancer

Phase 3 TALAPRO-3 results show that talazoparib plus enzalutamide significantly improves radiographic progression-free survival in HRR-mutated metastatic castration-sensitive prostate cancer, exceeding the target hazard ratio. Benefits were consistent across BRCA and non-BRCA subgroups, with a favorable safety profile and early signals of overall survival improvement, supporting earlier use of PARP inhibition in this high-risk population.

Pfizer announced positive topline results from the Phase 3 TALAPRO-3 study of talazoparib (TALZENNA), showing that its combination with enzalutamide (XTANDI) significantly improves outcomes in patients with homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC). The findings support a potential shift toward earlier use of poly ADP-ribose polymerase (PARP) inhibition in this high-risk population.

The randomized, double-blind, placebo-controlled study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS), compared with placebo plus enzalutamide. The observed benefit exceeded the predefined hazard ratio target of 0.63, with most patients remaining progression-free at the time of analysis. Importantly, efficacy was consistent across subgroups, including tumors harboring both BRCA and non-BRCA HRR alterations.

“Current treatment approaches leave many patients with HRR gene-mutated metastatic castration-sensitive prostate cancer vulnerable to early disease progression,” said Professor Neeraj Agarwal, M.D., FASCO, and global lead investigator for TALAPRO-3. “The TALAPRO-3 results demonstrate that treatment with TALZENNA in combination with XTANDI earlier in the disease course significantly extends the time patients can live without their cancer worsening.”

At interim analysis, a strong trend toward improved overall survival, OS, was observed, alongside favorable outcomes in key secondary endpoints such as overall response rate, duration of response, and time to prostate-specific antigen, PSA, progression. The safety profile of the combination was consistent with known data for each agent, with no new safety signals identified.

The trial enrolled 599 patients with HRR gene-mutated mCSPC across multiple global sites. Participants received either talazoparib 0.5 mg daily plus enzalutamide 160 mg daily, or placebo plus enzalutamide. Radiographic progression-free survival was defined according to RECIST 1.1 and PCWG3 criteria or death.

“Alterations in DNA damage repair genes, such as HRR genes, are found in approximately 25% of metastatic prostate cancers and associated with a worse prognosis and are less responsive to current standards of care, representing a group with a high unmet need,” said Jeff Legos, Chief Oncology Officer, Pfizer. “TALZENNA plus XTANDI is already a standard of care in HRR gene-mutated metastatic castration-resistant prostate cancer, and these unprecedented results demonstrate the potential to deliver benefit earlier in the disease course. These findings underscore Pfizer’s leadership in precision medicine and commitment to bringing more personalized treatment options to people living with prostate cancer.”

Currently approved for HRR-mutated metastatic castration-resistant prostate cancer, the talazoparib and enzalutamide combination is being evaluated for earlier-stage use. These data will be presented at an upcoming medical congress and discussed with regulatory authorities to support potential label expansion.