Talzenna Plus Xtandi Improves Radiographic Progression-Free Survival by More Than 50% in Metastatic Prostate Cancer – Pfizer

Pfizer  announced detailed results from the pivotal Phase 3 TALAPRO-3 study of Talzenna (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with Xtandi (enzalutamide), an androgen receptor pathway inhibitor (ARPI), in men with homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC). These results will be presented today in a late-breaking oral presentation (Abstract LBA5007) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in TheNew England Journal of Medicine.

Talzenna plus Xtandi  demonstrated a 52% reduction in the risk of radiographic progression or death compared to placebo plus Xtandi  (Hazard Ratio [HR] of 0.48; 95% Confidence Interval [CI], 0.36–0.65; p ˂ 0.0001). At three years, radiographic progression-free survival (rPFS) rates were estimated at 77% in patients treated with Talzenna plus Xtandi  versus 56% in patients treated with placebo plus Xtandi . With a median follow-up of over 37 months, median rPFS was not reached in the Talzenna plus Xtandi  arm and was 46 months with placebo and Xtandi .

The rPFS benefit observed with Talzenna plus Xtandi  was consistent across pre-specified groups with various patient and disease characteristics, including age, Gleason score, geographic region, prostate-specific antigen (PSA) level, and BRCA vs. non-BRCA HRR gene alteration status. At three years, rPFS rates were estimated at 77% vs. 49% in patients with cancer harboring BRCA alterations (HR, 0.37; 95% CI, 0.22–0.61) and 76% vs. 60% in patients with cancer with non-BRCA alterations (HR, 0.57; 95% CI, 0.39–0.82), compared with placebo plus Xtandi .

“Delaying progression to castration‑resistant disease, the most symptomatic and lethal phase of prostate cancer, remains a significant challenge to patients with mCSPC – especially to those with HRR gene alterations, who often experience poorer outcomes. With more than three years of follow‑up and median radiographic progression‑free survival not reached, Talzenna plus Xtandi  demonstrated durable disease control across a broad HRR‑altered population, including patients with BRCA and non‑BRCA alterations. These findings underscore the importance of genetic testing as part of routine care and highlight the potential for Talzenna plus Xtandi  to meaningfully improve the outcomes of patients with HRRm mCSPC.” – Neeraj Agarwal, M.D., FASCO, Presidential Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah and global lead investigator for TALAPRO-3.

Interim overall survival (OS) results showed a strong trend toward improved OS, a key secondary endpoint, with median OS not reached in either treatment arm (HR, 0.77; 95% CI, 0.56–1.04; p = 0.09). Talzenna plus Xtandi  also improved time to PSA progression (HR, 0.51; 95% CI, 0.37–0.71; p < 0.0001) and time to subsequent anti-cancer therapy (HR, 0.51; 95% CI, 0.38–0.70; p < 0.0001) vs. placebo plus Xtandi . The trial remains ongoing, and OS will be formally assessed at the final analysis.

In TALAPRO-3, the safety profile of Talzenna plus Xtandi  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.

Prostate cancer is the second most common cancer in men worldwide, with an estimated 1.5 million new cases diagnosed globally and 330,000 new cases anticipated in the United States in 2026. mCSPC is a form of advanced prostate cancer that has spread beyond the prostate but is still sensitive to androgen deprivation therapy. Approximately 5–10% of newly diagnosed cases are mCSPC, and up to 30% of these patients harbor HRR gene alterations.

Talzenna plus Xtandi  in HRR gene-mutated mCSPC is an investigational treatment regimen. The results from TALAPRO-3 are being discussed with global health authorities to potentially expand the combination regimen’s existing indication. Talzenna plus Xtandi  is currently approved in more than 60 countries, including in the U.S. for adults with HRR gene-mutated mCRPC and in the European Union for adults with mCRPC in whom chemotherapy is not clinically indicated.

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented at ASCO, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.