FDA expands TALZENNA plus XTANDI approval to earlier metastatic prostate cancer setting

Pfizer has received U.S. Food and Drug Administration approval to expand the use of TALZENNA in combination with XTANDI to an earlier stage of metastatic prostate cancer.

The combination is now approved for men with metastatic androgen pathway modulation-naïve or sensitive prostate cancer carrying homologous recombination repair gene mutations, including both BRCA and non-BRCA alterations.

The disease setting is also commonly referred to as metastatic hormone-sensitive prostate cancer.

The expanded indication allows TALZENNA, also known as talazoparib, to be used alongside XTANDI, or enzalutamide, before patients develop resistance to androgen pathway-directed treatment.

The FDA decision was supported by findings from the pivotal Phase III TALAPRO-3 study.

In the trial, TALZENNA plus XTANDI reduced the risk of radiographic disease progression or death by 52% compared with placebo plus XTANDI.

The radiographic progression-free survival hazard ratio was 0.48, with a 95% confidence interval of 0.36 to 0.65 and a p value below 0.0001.

At three years, an estimated 77% of patients receiving the TALZENNA combination remained free from radiographic progression.

Pfizer said the treatment benefit was observed across patients with BRCA mutations as well as those carrying other homologous recombination repair gene alterations.

Neeraj Agarwal, MD, global lead investigator for TALAPRO-3, said patients with newly diagnosed metastatic prostate cancer and HRR mutations can experience more aggressive disease and poorer outcomes.

He said the findings reinforce the importance of biomarker testing at diagnosis to identify patients who may benefit from targeted treatment earlier in the course of their disease.

TALZENNA is an oral poly ADP-ribose polymerase inhibitor, while XTANDI is an androgen receptor pathway inhibitor.

The combination was initially approved in the U.S. in 2023 for men with HRR-mutated metastatic castration-resistant prostate cancer, also referred to as metastatic androgen pathway modulation-resistant prostate cancer.

The latest decision therefore moves the combination into an earlier treatment setting before the development of resistance to androgen pathway modulation.

The safety profile in TALAPRO-3 was consistent with the established safety profiles of the individual medicines, with no new safety signals identified.

The most common treatment-emergent adverse events among patients receiving TALZENNA plus XTANDI included anaemia, fatigue, decreased neutrophil count and asthenia.

Anaemia was the most frequently reported Grade 3 or higher treatment-emergent adverse event, occurring in 51% of patients receiving TALZENNA plus XTANDI compared with 3% of patients in the control group.

Five percent of patients discontinued TALZENNA because of anaemia.

Pfizer said adverse events were generally managed through dose adjustments and supportive care.

Aamir Malik, Executive Vice President and Chief U.S. Commercial Officer at Pfizer, said moving the combination into an earlier metastatic setting provides another treatment option for men with HRR-mutated disease at a stage where delaying progression may have greater impact.

The TALAPRO-3 results were previously presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.

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