Global pharma giant Pfizer has announced that its Phase 3 TALAPRO-3 study has delivered positive topline results, showing that TALZENNA (talazoparib) combined with XTANDI (enzalutamide) significantly improves outcomes for patients with HRR gene-mutated metastatic castration-sensitive prostate cancer (mCSPC).
The study hit its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared to placebo plus XTANDI. The results exceeded the pre-specified target hazard ratio of 0.63, with most patients remaining progression-free at the time of analysis. Benefits were consistent across tumors 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 analysis also showed a strong trend toward improved overall survival, a key secondary endpoint. Additional secondary endpoints, including overall response rate, duration of response, and time to PSA progression, also favored the combination therapy. Safety was consistent with known profiles of the individual drugs, with no new safety signals identified.
Prostate cancer remains the second most common cancer in men worldwide, with an estimated 1.4 million new cases diagnosed globally in 2022 and 330,000 new cases anticipated in the U.S. in 2026. Despite treatment advances, 50% to 65% of mCSPC patients progress to metastatic castration-resistant prostate cancer (mCRPC) within two years, particularly those with HRR gene mutations.
“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 at 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.”
