FDA Approves Talazoparib/Enzalutamide in HRR-Mutant mCRPC

"TALAPRO-2 is the first phase 3 study to evaluate talazoparib plus enzalutamide as a first-line treatment in patients with metastatic castration resistant prostate cancer," according to lead study author Arun Azad, MBBS, PhD, FRACP, a medical oncologist at Peter MacCallum Cancer Centre, Australia.

The FDA has approved a combination of talazoparib (Talzenna) and enzalutamide for the treatment of homologous recombination repair (HRR) gene–mutant metastatic castration-resistant prostate cancer (mCRPC), according to a press release from the regulatory agency.¹

The agent’s efficacy was evaluated as part of the phase 3 TALAPRO-2 (NCT03395197) trial,² in which 399 patients with HRR gene–mutant mCRPC were randomly assigned 1:1 to be treated with 160 mg of enzalutamide plus 0.5 mg of either talazoparib or placebo.

These and other findings from the trial were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The experimental regimen resulted in a significantly improved radiographic progression-free survival (rPFS), the median of which was not reached, compared with a median of 13.8 months in the placebo arm (Hazard ratio [HR], 0.45; 95% CI, 0.33-0.61; P <.0001). When rPFS was assessed in patients with BRCA-mutant disease, investigators reported an HR of 0.20 (95% CI, 0.11-0.39) compared with 0.72 (95% CI, 0.49-1.07) in the non-BRCA–mutant population.

“TALAPRO-2 is the first phase 3 study to evaluate talazoparib plus enzalutamide as a first-line treatment in patients with metastatic castration resistant prostate cancer, or mCRPC…. Here we provide a detailed overview of the safety profile of talazoparib plus enzalutamide in the all-comers population of the TALAPRO-2 trial, with the aim of understanding how adverse events were managed,” lead study author Arun Azad, MBBS, PhD, FRACP, a medical oncologist at Peter MacCallum Cancer Centre, Australia, said in a presentation of the findings.

According to the press release, there are several adverse effects commonly associated with the regimen, including “decreased hemoglobin, decreased neutrophils, decreased lymphocytes, fatigue, decreased platelets, decreased calcium, nausea, decreased appetite, decreased sodium, decreased phosphate, fractures, decreased magnesium, dizziness, increased bilirubin, decreased potassium, and dysgeusia.”

Among those who were treated with talazoparib and enzalutamide, 39% needed a blood transfusion and 22% needed multiple transfusions. Additionally, 2 patients were diagnosed with myelodysplastic syndrome/acute myeloid leukemia.

References

1. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. News release. FDA. June 20, 2023. Accessed June 21, 2023. https://bit.ly/3pcuSTH
2. Azad A, Fizazi K, Matsubara N, et al. Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): safety analyses from the randomized, placebo (PBO)-controlled, phase 3 TALAPRO-2 study. J Clin Oncol. 2023;41(suppl 16):5053. doi:10.1200/JCO.2023.41.16_suppl.5053