NEW YORK – The US Food and Drug Administration on Tuesday approved Pfizer's PARP inhibitor Talzenna (talazoparib) plus its androgen receptor inhibitor Xtandi (enzalutamide) for patients with metastatic castration-resistant prostate cancers harboring homologous recombination repair deficiencies.
The FDA reviewed the results of the Phase III TALAPRO-2 clinical trial, in which Pfizer randomized nearly 400 patients to either Xtandi plus Talzenna or Xtandi plus placebo. In a biomarker-defined cohort of patients whose cancers had mutations in the HRR genes ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C, Talzenna plus Xtandi reduced the risk of disease progression or death by 55 percent compared to those in the other arm.
The approval in this biomarker-defined patient population comes after Pfizer initially tried seeking FDA approval for the combination regimen in an all-comer patient population. The drugmaker had said in February that it was seeking approval in the broader population because a progression-free survival benefit was seen in all patients on Talzenna-Xtandi, regardless of HRR gene mutation status.
However, at the time oncologists were concerned that the benefit in the biomarker-defined subgroup might be driving the benefit seen in the study. When Pfizer reported the benefit in the HRR-altered subgroup earlier this month, that concern was again top of mind for oncologists.
The overall survival data from TALAPRO-2 won't read out until next year, but Pfizer said in a statement on Tuesday that those data "may be used to support a potential regulatory filing to benefit broader patient populations."
The regulatory story for Talzenna-Xtandi in mCRPC is similar to that of Merck and AstraZeneca's Lynparza (olaparib) in the same setting. Initially, drugmakers sought FDA approval for their PARP inhibitor with Janssen's androgen receptor inhibitor Zytiga (abiraterone) in an all-comer mCRPC population, but the FDA approved the combination only for patients with BRCA1/2 mutations.
Pfizer has also submitted the TALAPRO-2 data to regulators in Europe and other countries.