FDA approves Talzenna regimen for certain men with metastatic prostate cancer
FDA approved talazoparib plus enzalutamide for treatment of homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer.
The agency based the approval on results of TALAPRO-2, a randomized phase 3, two-part study that evaluated efficacy of talazoparib (Talzenna, Pfizer), a poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with enzalutamide (Xtandi; Astellas, Pfizer), a potent androgen receptor signaling inhibitor.
Cohort 2 of the study enrolled 399 men with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer who had no previous systemic therapy for castration-resistant disease.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” Neeraj Agarwal, MD, FASCO, presidential endowed chair of cancer research and director of the genitourinary oncology program at Huntsman Cancer Institute at University of Utah, and global lead investigator of TALAPRO-2, said in a Pfizer press release. “Therefore, new first-line treatment options are needed to reduce the risk [for] disease progression or death.”
Researchers randomly assigned the men to 160 mg daily enzalutamide plus either 0.5 mg daily talazoparib or placebo.
Radiographic PFS per blinded independent central review served as the major efficacy outcome measure.
Results showed significantly longer radiographic PFS with the talazoparib combination vs. placebo and enzalutamide among men with HRR gene mutations (median, not reached vs. 13.8 months; HR = 0.45; 95% CI, 0.33-0.61). An exploratory analysis showed HRs for radiographic PFS of 0.2 (95% CI, 0.11-0.36) among 155 men with BRCA-mutated disease and 0.72 (95% CI, 0.49-1.07) among men with non-BRCA-mutated HRR gene-mutated disease.
The talazoparib-enzalutamide combination exhibited a safety profile generally consistent with that of each individual agent. The most common adverse events included decreased hemoglobin, decreased neutrophils, decreased lymphocytes, fatigue, decreased platelets, decreased calcium, nausea and decreased appetite. Nearly one-third of patients (30%) who received the regimen experienced serious adverse reactions, including anemia and fracture, and 10% of patients discontinued talazoparib.
The combination “represents a treatment option deserving of excitement and attention,” Agarwal said in the Pfizer press release.
Final OS data from the trial are expected next year, according to Pfizer.
References:
- FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer (press release). Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-enzalutamide-hrr-gene-mutated-metastatic-castration-resistant-prostate. Published June 20, 2023. Accessed June 21, 2023.
- Pfizer’s Talzenna in combination with Xtandi receives U.S. FDA approval (press release). Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizers-talzennar-combination-xtandir-receives-us-fda. Published June 20, 2023. Accessed June 21, 2023.