Pfizer Inc. 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 The New 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 harbouring 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,” 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 (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 anaemia, reported by 51% in the Talzenna plus Xtandi group and 3% in the control group. Five percent of patients discontinued Talzenna due to anaemia. TEAEs 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 is still sensitive to androgen deprivation therapy. Approximately 5–10% 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 to potentially expand the combination regimen’s existing indication. 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.
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.
The phase 3 TALAPRO-3 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 599 patients with mCSPC (with =3 months of ADT [chemical or surgical] with or without an approved ARPI in the mCSPC setting) at sites in the US, Canada, Europe, South America, and the Asia-Pacific region. Patients with histologically/cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small cell, or signet cell features and with alterations in one or more HRR genes (as per HRR12 gene panel) in the trial were randomized to receive Talzenna 0.5 mg/day plus Xtandi 160mg/day, or placebo plus Xtandi 160mg/day.
The primary endpoint of the trial 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 Tumours 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. Secondary endpoints include OS, objective response rate, duration of response, and patient-reported outcomes.
Talzenna is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that Talzenna blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.
Talzenna was initially approved in the US, EU, and multiple other regions as a single agent for the treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer.
Talzenna in combination with Xtandi was approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. Talzenna in combination with Xtandi is approved in more than 60 countries, indications vary by country.
Talzenna is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:
HRR gene-mutated mCRPC:
- In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Breast cancer:
- As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for Talzenna.
Xtandi (enzalutamide) is an androgen receptor pathway inhibitor. Xtandi is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). Xtandi is currently approved for one or more of these indications in more than 80 countries, including in the United States, European Union and Japan. Over 1.5 million patients have been treated with Xtandi globally.
Xtandi (enzalutamide) is indicated for the treatment of patients with:
- castration-resistant prostate cancer (CRPC)
- metastatic castration-sensitive prostate cancer (mCSPC)
- nonmetastatic castration sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
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