FDA Expands Approval of Talzenna Plus Xtandi for HRR Gene-Mutated Metastatic Hormone-Sensitive Prostate Cancer – Pfizer

Pfizer Inc. announced that the FDA has expanded approval of Talzenna (talazoparib) in combination with Xtandi (enzalutamide) to the treatment of men with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with homologous recombination repair gene mutations, including both BRCA and non-BRCA mutations. mAPMN/S is also known as metastatic hormone-sensitive prostate cancer .

This approval makes Talzenna, an oral poly ADP-ribose polymerase (PARP inhibitor), plus Xtandi, an androgen receptor pathway inhibitor (ARPI), available in an earlier line, providing an opportunity to delay disease progression at a critical stage when more patients may experience greater benefit.

“Today’s approval of Talzenna plus Xtandi builds on its established role as a standard-of-care option for men with advanced prostate cancer. Moving this targeted therapy into the androgen pathway modulation-naïve or -sensitive setting further reflects our commitment to men with HRR-mutated metastatic prostate cancer, providing a new option at a stage where it may have a greater impact to delay progression.” – Aamir Malik, Executive Vice President, Chief U.S. Commercial Officer, Pfizer.

“This approval represents a critical advancement for patients with newly diagnosed metastatic prostate cancer with HRR gene mutations, who face a more aggressive disease, worse prognosis, and limited treatment options. In the TALAPRO-3 trial, clinical benefits were consistent for patients with BRCA and non-BRCA HRR gene mutations, addressing a long-standing unmet need – and reinforcing the importance of biomarker testing at the time of diagnosis.” – Neeraj Agarwal, M.D., FASCO, Co-director of Prostate Cancer Program at Harvard Cancer Consortium, faculty medical oncologist at Dana-Farber Cancer Institute, and global lead investigator for TALAPRO-3.

Talzenna plus Xtandi was first approved in the U.S. in 2023 for men with metastatic androgen pathway modulation resistant (mAPMR) PC with HRR gene mutations, also known as HRRm metastatic castration-resistant prostate cancer (mCRPC). The application to expand the indication was reviewed under FDA Priority Review and was supported by results from the Phase 3 TALAPRO-3 study.

Key Results from the Pivotal Phase 3 TALAPRO-3 Study

– Improved Radiographic Progression-Free Survival (rPFS): Talzenna plus Xtandi reduced the risk of radiographic progression or death by 52% vs. placebo plus Xtandi (Hazard Ratio [HR] of 0.48; 95% Confidence Interval [CI], 0.36–0.65; p < 0.0001) in patients with mAPMN/S PC with HRR gene mutations and an estimated 77% of patients remained progression-free at three years. Consistent benefit was observed across patients with BRCA and non-BRCA HRR gene mutations.

– Consistent Safety Profile: The safety profile was consistent with the known profiles of each agent, and no new safety signals were identified. The most common treatment-emergent adverse events (TEAEs) in the Talzenna plus Xtandi group were anemia, fatigue, decreased neutrophil count, and asthenia. The most common grade 3 or higher TEAE was anemia, reported by 51% in the Talzenna plus Xtandi group and 3% in the control group. Five percent of patients discontinued Talzenna due to anemia. TEAEs were generally manageable with dose modifications and supportive care as needed.

– Published Previously: These results were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

About the TALAPRO-3 Phase 3 Study

• TALAPRO-3 (NCT04821622) is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 599 patients with mAPMN/S PC with ≤3 months of androgen deprivation therapy (ADT) [chemical or surgical] with or without an approved ARPI in the mAPMN/S setting at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region.
• Patients were randomized to receive Talzenna 0.5 mg/day plus Xtandi 160mg/day, or placebo plus Xtandi 160mg/day.
• The primary endpoint is investigator-assessed rPFS, defined as the time from the date of randomization to radiographic progression in soft tissue per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or in bone per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator assessment, or death, whichever occurs first.