Pfizer’s TALZENNA–XTANDI Combo Shows Strong Phase III Results In HRR-Mutated Metastatic Prostate Cancer, With Significant Progression-Free Survival Benefit

Pfizer Inc. announced positive topline findings from the Phase III TALAPRO-3 trial evaluating TALZENNA® (talazoparib) combined with XTANDI® (enzalutamide) for patients with homologous recombination repair (HRR) gene–mutated metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer. The study assesses the PARP inhibitor and androgen receptor pathway inhibitor combination as a potential earlier-line treatment option.

The trial achieved its primary endpoint, showing that TALZENNA plus XTANDI significantly improved radiographic progression-free survival compared with placebo plus XTANDI. Outcomes surpassed the predefined hazard ratio target, with most participants remaining progression-free at the time of evaluation. Treatment benefits were consistent across patients with both BRCA and non-BRCA HRR gene alterations.

“Current treatment approaches leave many patients with HRR gene-mutated metastatic castration-sensitive prostate cancer vulnerable to early disease progression,” said Neeraj Agarwal, M.D., FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah, 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.”

Interim data also indicated a favorable trend toward improved overall survival, a key secondary endpoint. Additional secondary measures, including overall response rate, duration of response, and time to prostate-specific antigen progression, also favored the combination regimen. Safety findings aligned with the established profiles of both therapies, with no new safety concerns reported.

“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.”

Prostate cancer remains the second most commonly diagnosed cancer in men worldwide, and patients with mCSPC frequently progress to more aggressive metastatic castration-resistant disease, particularly those with HRR gene mutations. The TALZENNA–XTANDI combination for HRR gene–mutated mCSPC remains investigational, with results planned for presentation at a forthcoming medical meeting and discussions underway with regulators regarding potential filings. The regimen is already approved in around 60 countries for specific metastatic castration-resistant prostate cancer indications.