The U.S. FDA expanded approval for Pfizer's PARP inhibitor talazoparib (Talzenna) combined with enzalutamide (Xtandi) to treat adult patients with HRR gene-mutated metastatic hormone-sensitive prostate cancer. Based on the Phase 3 TALAPRO-3 trial of 599 patients, the combination reduced the risk of radiographic progression or death by 52% compared to placebo plus enzalutamide. Grade 3 or higher anemia occurred in 51% of combination patients, with 5% discontinuing talazoparib.
FDA approval and regulatory review
- ▪The FDA's expanded approval of talazoparib plus enzalutamide for HRR gene-mutated metastatic hormone-sensitive prostate cancer covers patients with both BRCA and non-BRCA HRR gene mutations based on consistent clinical benefits observed in the TALAPRO-3 trial
- ▪The U.S. FDA expanded its approval of Pfizer's PARP inhibitor talazoparib in combination with enzalutamide to treat adult patients with HRR gene-mutated metastatic androgen pathway modulation-naïve or -sensitive prostate cancer
- ▪The FDA previously authorized FoundationOne CDx and FoundationOne Liquid CDx assays as companion diagnostic devices to identify HRR gene mutations for talazoparib plus enzalutamide treatment
- ▪The FDA reviewed Pfizer's supplemental application for talazoparib plus enzalutamide under Priority Review and Project Orbis
- ▪The FDA first approved talazoparib in combination with enzalutamide in June 2023 for patients with HRR gene-mutated metastatic castration-resistant prostate cancer
TALAPRO-3 trial design and endpoints
- ▪The primary endpoint of the TALAPRO-3 trial was investigator-assessed radiographic progression-free survival evaluated per RECIST 1.1 soft tissue and PCWG3 bone criteria
- ▪In the Phase 3 TALAPRO-3 trial, patients were randomized to receive 0.5 mg daily talazoparib plus 160 mg daily enzalutamide or placebo plus enzalutamide, along with continuous androgen deprivation therapy
- ▪The Phase 3 TALAPRO-3 study enrolled 599 patients with HRR gene-mutated metastatic androgen pathway modulation-naïve or -sensitive prostate cancer across U.S., Canadian, European, South American, and Asia-Pacific sites
Radiographic progression-free survival outcomes
- ▪In the TALAPRO-3 trial, median radiographic progression-free survival was 45.8 months in the placebo arm and not reached with talazoparib plus enzalutamide, with an estimated 77% versus 56% remaining progression-free at three years of follow-up
- ▪In the TALAPRO-3 trial, talazoparib plus enzalutamide reduced the risk of radiographic progression or death by 52% compared to placebo plus enzalutamide in patients with HRR-mutated prostate cancer
Anemia and transfusion safety findings
- ▪In a pooled safety analysis of 810 prostate cancer patients receiving talazoparib with enzalutamide, 41% required red blood cell transfusions, with 25% requiring multiple transfusions
- ▪In the TALAPRO-3 trial, 51% of patients receiving talazoparib plus enzalutamide experienced Grade 3 or higher anemia compared to 3% in the placebo control arm, with 5% permanently discontinuing talazoparib therapy due to anemia
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