The U.S. Food and Drug Administration (FDA) approved updated labeling for Talzenna (talazoparib) plus Xtandi (enzalutamide) for men with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, but did not expand its use to non-HRR gene mutations, according to a news release from Pfizer.
The FDA’s decision to update the label for Talzenna and Xtandi was based on data from the phase 3 TALAPRO-2 trial. Results showed a statistically significant and clinically meaningful improvement in overall survival for this group. At a median follow-up of 44.2 months, median overall survival was 45.1 months for those receiving Talzenna and Xtandi versus 31.1 months in the Xtandi and placebo group; this translates to a 14-month improvement and a 38% reduction in the risk of death.
However, the FDA also stated that the trial did not support expanding the indication to include patients without these mutations, and Pfizer will not pursue that expansion in the United States.
For more information on the trial and efficacy results, watch Dr. Chandler Park, a medical oncologist of Genitourinary Medical Oncology, at the Norton Healthcare Institute, in Louisville, Kentucky, discuss the TALAPRO-2 trial as the biggest takeaway from the 2025 Annual ASCO Genitourinary (GU) Cancers Symposium in terms of prostate cancer treatment.
“Men with metastatic castration-resistant prostate cancer are often faced with a poor prognosis and limited treatment options, and Talzenna in combination with Xtandi has redefined the standard-of-care for patients living with HRR gene-mutated metastatic castration-resistant prostate cancer,” Dr. Johanna Bendell, oncology chief development officer, Pfizer, said in the news release. “We are pleased that the statistically significant final overall survival data reaffirming the current indication has been added to the label, based on the strong results from TALAPRO-2.”
Glossary:
Overall survival: time from treatment start until death from any cause.
Radiographic progression-free survival: time from randomization until radiographic evidence of cancer progression or death.
Objective response rate: percentage of patients whose cancer shrinks or disappears after treatment.
Duration of response: length of time cancer remains controlled after initial response to treatment.
Prostate-specific antigen response: reduction in prostate-specific antigen levels indicating treatment effectiveness.
The phase 3 TALAPRO-2 trial evaluated treatment for metastatic castration-resistant prostate cancer in patients who had not received newer life-prolonging therapies. This global study enrolled 1,035 patients across the U.S., Canada, Europe, South America and the Asia-Pacific region. Participants were divided into two groups: an unselected group of 805 patients, which included 169 with homologous recombination repair gene mutations, and a second group of 399 patients with HRR mutations, combining the 169 from the first group with 230 additional patients. Patients were randomly assigned to receive either Talzenna with Xtandi or a placebo with Xtandi.
Overall survival was a planned key secondary endpoint in the study. The primary end point was radiographic progression-free survival, measured from randomization to the first radiographic progression or death. This applied to both the unselected group and the group with homologous recombination repair mutations. Other secondary end points included objective response rate, duration of response, prostate-specific antigen response, time to chemotherapy and progression-free survival after the next treatment.
What is Talzenna and its Previous FDA Indications?
Talzenna (talazoparib) is an oral drug that blocks poly ADP-ribose polymerase, an enzyme involved in repairing damaged DNA. By inhibiting this enzyme and trapping it at sites of DNA damage, Talzenna reduces cancer cell growth and leads to cancer cell death. This action makes it effective against cancers with defects in DNA repair.
Talzenna was first approved as a single treatment for adults with HER2-negative locally advanced or metastatic breast cancer who have harmful or suspected harmful germline BRCA mutations. Patients are selected for this treatment based on a government-approved test that detects these mutations.
In June 2023, the FDA approved Talzenna combined with Xtandi for adults with metastatic castration-resistant prostate cancer that has mutations in homologous recombination repair genes. This combination works by targeting both DNA repair pathways and androgen receptor signaling to slow cancer growth. The European Commission followed with approval in January 2024 for patients with metastatic castration-resistant prostate cancer who are not candidates for chemotherapy. Talzenna is the first drug of its kind approved in the European Union to be used with Xtandi for prostate cancer, regardless of gene mutation status.
Today, Talzenna plus Xtandi is approved in more than 40 countries worldwide for advanced prostate cancer, though exact uses differ by region. This combination provides a new treatment option for patients with advanced prostate cancer who have limited therapies available, as per the release.
Reference:
“Pfizer provides update on U.S. regulatory review of Talzenna in combination with Xtandi for broader use in metastatic castration-resistant prostate cancer,” Pfizer Inc., June 13, 2025.
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