NEW YORK, United States — October 26, 2026
Pfizer Inc., a global biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has expanded approval of TALZENNA® (talazoparib) in combination with XTANDI® (enzalutamide) for adult men with homologous recombination repair (HRR) gene-mutated metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer, also known as metastatic hormone-sensitive prostate cancer (mHSPC). The approval makes the combination available at an earlier stage of metastatic disease, including for patients with BRCA and non-BRCA HRR gene mutations detected by an FDA-authorized test. TALZENNA is an oral poly ADP-ribose polymerase (PARP) inhibitor that targets DNA damage repair mechanisms, while XTANDI is an androgen receptor pathway inhibitor (ARPI). The FDA decision was supported by results from the pivotal Phase III TALAPRO-3 study and followed a Priority Review. The combination was previously approved in the United States in 2023 for HRR gene-mutated metastatic androgen pathway modulation-resistant prostate cancer. Pfizer said the expanded indication reflects its focus on bringing precision medicines into earlier treatment settings, where delaying disease progression may provide meaningful benefits for eligible patients..
TALAPRO-3 Study Demonstrates Significant Reduction in Disease Progression
The Phase III TALAPRO-3 study evaluated TALZENNA plus XTANDI against placebo plus XTANDI in 599 patients with HRR gene-mutated mAPMN/S prostate cancer. The randomized, double-blind, placebo-controlled trial enrolled participants across sites in North America, Europe, South America and the Asia-Pacific region. Patients received TALZENNA at 0.5 mg daily alongside XTANDI at 160 mg daily, or placebo alongside XTANDI. The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS), measuring the time until radiographic disease progression or death. According to Pfizer, the combination reduced the risk of radiographic progression or death by 52% compared with XTANDI alone, with a hazard ratio of 0.48 (95% confidence interval: 0.36–0.65; p less than 0.0001). An estimated 77% of patients receiving the combination remained progression-free at three years. Consistent treatment benefits were observed among patients with both BRCA and non-BRCA HRR gene mutations, highlighting the importance of identifying relevant biomarkers when planning treatment. The results were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in The New England Journal of Medicine.
Safety Profile Highlights the Need for Blood Count Monitoring
The safety findings from TALAPRO-3 were consistent with the known profiles of TALZENNA and XTANDI, and Pfizer reported no new safety signals. The most common treatment-emergent adverse events in the combination group included anemia, fatigue, decreased neutrophil count and asthenia. Grade 3 or higher anemia was reported in 51% of patients receiving TALZENNA plus XTANDI, compared with 3% in the control group, and 5% of patients discontinued TALZENNA because of anemia. The company reported that adverse events were generally managed through dose modifications and supportive care when needed. TALZENNA carries important warnings, including the risk of myelosuppression and myelodysplastic syndrome or acute myeloid leukemia (MDS/AML), which have occurred rarely and, in some cases, been fatal. Blood counts should be monitored monthly during treatment, with additional evaluation and treatment interruption where clinically indicated. XTANDI also has important safety considerations, including seizure risk, posterior reversible encephalopathy syndrome, ischemic heart disease, falls and fractures. These risks require assessment and monitoring by healthcare professionals. Treatment selection and management should follow the approved prescribing information, taking account of individual patient risks, concomitant medications and clinical needs.
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Expanded FDA Approval Advances Pfizer’s Precision Oncology Strategy
The expanded indication strengthens Pfizer’s position in genitourinary cancers by making the TALZENNA and XTANDI combination available to eligible patients earlier in the course of metastatic prostate cancer. HRR gene mutations are estimated to occur in approximately 25% of patients with mAPMN/S prostate cancer, making biomarker testing an important consideration in treatment planning. Pfizer stated that the approval reflects its long-standing commitment to advancing therapies for genitourinary cancers and addressing unmet needs through precision medicine. The FDA reviewed the application under Project Orbis, an initiative designed to support coordinated review of oncology medicines among participating international regulatory authorities. A corresponding application is under review by the European Medicines Agency, while additional global regulatory filings are planned or underway. The combination is already approved in multiple countries for certain forms of advanced prostate cancer, although authorized indications vary by region. The new U.S. indication expands its role beyond metastatic disease that has become resistant to androgen pathway modulation to include hormone-sensitive disease with HRR gene mutations. As clinicians integrate genomic testing and treatment options into care pathways, the combination may offer an additional approach to delaying progression in this patient population. Its use remains dependent on the approved indication, biomarker status and individual clinical assessment.
Source: Pfize, Press release
