FDA sees issues with the drug company’s application for expanding the use of talazoparib.
Pfizer was taken to task at a recent meeting of the US Food and Drug Administration ’s Oncologic Drugs Advisory Committee for attempting to expand the use of its prostate cancer drug talazoparib to men lacking a key biomarker without providing sufficient evidence of benefit.
“It’s tantamount to somebody shooting an arrow on the wall and then painting a target around it,” and that the attempt “is not consistent with a large pharmaceutical company presentation to an advisory committee,” saidin combination with enzalutamide for men with homologous recombination repair mutated metastatic castration–resistant prostate cancer based on a progression-free survival benefit vs placebo in the TALAPRO-2 trial.better overall survival not only in men who had the mutation but also in 805 individuals whose HRR mutation status wasn’t known at baseline. In an exploratory analysis, the company found a trend toward better OS among the men in the group who didn’t have the mutation. Pfizer is seeking an “all comers” approval based on the results; if granted, the indication for talazoparib would effectively be expanded to include the 70% of patients with metastatic castration–resistant prostate cancer who are HRR mutation free.Among FDA’s concerns, is that agency analysts found no OS benefit among nonmutated men when they used a different HRR status measurement than Pfizer . They also noted that adding talazoparib to enzalutamide markedly increases toxicity; approximately 40% of men on the combination, for instance, require blood transfusions for anemia.However, the FDA’s main concern with Pfizer’s efforts is that TALAPRO-2 wasn’t specifically designed and powered to show that talazoparib works in men who don’t have an HRR mutation. There was no prespecified alpha-controlled testing plan, meaning that “the favorable trend in PFS and OS in this subgroup can be a random false positive,” the agency said in a “To put the elephant in the room,” Pazdur explained, Pfizer’s attempt to gain a mutation-agnostic indication based on TALAPRO-2 “is like somebody coming to us with a randomized study, having it completed, and saying ‘oops, I forgot to do a statistical analysis plan.’ We do not have confidence” in the results. “This is not just a pin-headed issue of statistics,” he continued. “It’s really where the rubber meets the road. As a federal agency, we have to protect the patient’s rights,” and “people have a right to know” how well a treatment is expected to work for them. FDA presenters noted instances of studies with promising subgroup findings like TALAPRO-2 that fell apart in later randomized trials. That’s why to expand an indication to include “a huge” number of new patients, “you need robust proof,” Pazdur said.ODAC was convinced by the FDA’s arguments. The eight panellists voted unanimously that TALAPR0-2 is not sufficient to conclude a favorable benefit-risk profile for talazoparib in patients with prostate cancer who aren’t HRR mutated. They also agreed with FDA’s broader assertion that cancer drug “efficacy should be formally evaluated in a biomarker-negative population when the biomarker is predictive of response and the prevalence of the biomarker-negative group is high.”“We need to commit to formally evaluating whether targeted therapies benefit patients without the biomarker and not try to ascertain this in some sort of ad hoc way,” he said. As for the benefit of talazoparib in men who don’t have an HRR mutation, “we just don’t know from this dataset,” saidM. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email:Medscape All material on this website is protected by copyright, Copyright © 1994-2025 by WebMD LLC. This website also contains material copyrighted by 3rd parties.
Malignant Prostate Neoplasm Prostate Cancer Cancer Of The Prostate U.S. Food And Drug Administration United States Food And Drug Administration FDA Food And Drug Administration (FDA) Food And Drug Administration Biomarker Biological Marker Multi-Biomarker Disease Activity MBDA Multibiomarker Disease Activity Breast Cancer Malignant Breast Neoplasm
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