The FDA’s independent advisors found Pfizer’s data lacked the precision needed to establish the efficacy of Talzenna in patients with prostate cancer who do not carry HRR mutations.
The FDA’s Oncologic Drugs Advisory Committee unanimously declined to endorse a label expansion for Pfizer’s PARP inhibitor Talzenna, which the pharma is proposing as a combination regimen with its drug Xtandi for first-line treatment of patients with metastatic castration-resistant prostate cancer carrying a certain biomarker profile.
Voting 8–0 against the proposal, the external experts said Wednesday that Pfizer had not provided enough evidence to establish the efficacy of the Talzenna combo in men with non-homologous recombination repair mutated (non-HRRm) prostate cancer.
“Precision oncology demands precision trials,” Neil Vasan, assistant professor at the Columbia University Medical Center, said at the end of the meeting explaining his no vote. “The study was not powered to test the efficacy in the patients without HRR mutations,” which in turn “weakened the strength of the conclusions that we can draw.”
This problem extends “across all oncology” as well, Vasan added. “As a field, we need to commit to formally evaluating whether targeted therapies benefit patients with and without the biomarker.”
To back its latest application, which seeks a broader prostate cancer label for Talzenna, Pfizer drew data from the Phase III TALAPRO-2 trial. The company announced in October 2024 that Talzenna plus Xtandi significantly and meaningfully improved overall survival (OS) versus Xtandi alone—an effect that was observed not only in those with HRR mutation but in all participants regardless of biomarker status.
At the time, Roger Dansey, former chief oncology officer at Pfizer, said that Talzenna is the “first and only PARP inhibitor” to demonstrate a significant survival benefit, when used with an androgen receptor blocker, in mCRPC patients, “regardless of mutation status.”
But in a briefing document published ahead of the advisory committee meeting, the FDA’s internal reviewers challenged Dansey’s claims. “While the statistically significant OS improvement in the all-comers population provided the impetus for this application, interpretation of the OS result and its applicability to current U.S. standard of care are unclear,” they wrote. “Consideration of the all-comers OS result may be misleading when interpreting efficacy in the non-HRRm population.”
Talzenna, an oral drug, was first approved by the FDA in October 2018 for HER2-negative, germline BRCA-mutated breast cancer. Nearly five years later, in June 2023, the agency handed Talzenna a label expansion, this time in combination with Xtandi, an oral androgen receptor blocker, for patients with metastatic castration-resistant prostate cancer (mCRPC) who have HRR mutations.
