TALZENNA and XTANDI combination cuts radiographic disease progression risk by over half in metastatic prostate cancer

The combination is the first PARP inhibitor plus ARPI regimen to deliver consistent radiographic progression free survival improvement in HRR gene altered metastatic hormone sensitive prostate cancer, across both BRCA and non BRCA alterations. There was an estimated 77% probability of remaining progression free at three years with TALZENNA plus XTANDI. Detailed results from the pivotal TALAPRO-3 study have been presented at ASCO 2026 and published in The New England Journal of Medicine.

Pfizer has shared 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). The findings will be presented in a late breaking oral presentation (Abstract LBA5007) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in The New England Journal of Medicine.

TALZENNA plus XTANDI produced a 52% reduction in the risk of radiographic progression or death versus placebo plus XTANDI (hazard ratio 0.48; 95% confidence interval 0.36 to 0.65; p<0.0001). At three years, radiographic progression free survival rates were estimated at 77% for patients on TALZENNA plus XTANDI, compared with 56% for those on placebo plus XTANDI. With a median follow up of more than 37 months, median radiographic progression free survival had not been reached in the TALZENNA plus XTANDI arm, versus 46 months in the placebo and XTANDI arm.

The radiographic progression free survival benefit seen with TALZENNA plus XTANDI was consistent across pre specified groups defined by patient and disease characteristics, including age, Gleason score, geographic region, prostate specific antigen (PSA) level, and BRCA versus non BRCA HRR gene alteration status. At three years, radiographic progression free survival rates were estimated at 77% versus 49% in patients with cancers harbouring BRCA alterations (hazard ratio 0.37; 95% confidence interval 0.22 to 0.61), and 76% versus 60% in patients with non BRCA alterations (hazard ratio 0.57; 95% confidence interval 0.39 to 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,” said 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. “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.”

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

In TALAPRO-3, the safety profile of TALZENNA plus XTANDI remained consistent with the known profiles of each agent, and no new safety signals were identified. The most common treatment emergent adverse events in the TALZENNA plus XTANDI group were anaemia, fatigue, decreased neutrophil count, and asthenia. The most common grade 3 or higher treatment emergent adverse event was anaemia, reported in 51% of patients on TALZENNA plus XTANDI and 3% of those in the control group. Five percent of patients discontinued TALZENNA due to anaemia. Treatment emergent adverse events were generally manageable with dose modifications and supportive care as needed.

“Men with HRR gene-mutated metastatic prostate cancer face significant challenges, with faster disease progression and limited treatment options, making it critical to intervene as early in the course of disease as possible,” said Jeff Legos, Chief Oncology Officer, Pfizer. “The benefit seen with TALZENNA plus XTANDI across a full spectrum of HRR gene alterations reinforces its potential to fundamentally change clinical practice, giving patients significantly more time before disease progression as compared to the current standard of care.”

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 remains sensitive to androgen deprivation therapy. Around 5 to 10% of newly diagnosed cases are mCSPC, and up to 30% of these patients harbour 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 with the aim of potentially expanding the existing indication for the combination. TALZENNA plus XTANDI is currently approved in more than 60 countries, including in the US for adults with HRR gene mutated mCRPC and in the European Union for adults with mCRPC in whom chemotherapy is not clinically indicated.

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Related Topics and Keywords

metastatic prostate cancer, Pfizer, radiographic disease, talzenna, XTANDI®