Study Investigates Risk of Hematological AEs After Talazoparib Regimen for mCRPC

A safety analysis of the TALAPRO-2 trial, which assessed the combination of talazoparib and enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC), was presented at the Hematology/Oncology Pharmacy Association Annual Conference 2024. The study looked at the relationship between talazoparib exposure and risk of severe anemia, thrombocytopenia, and neutropenia.

In the phase 3 TALAPRO-2 trial, “hematologic [adverse events (AEs)] such as anemia, thrombocytopenia, and neutropenia were the most common AEs leading to dose interruptions or reductions,” the authors wrote. In this analysis of 412 patients, they assessed potential prognostic factors and time to first incidence of grade ≥3 hematological AEs. The study consisted of patients from the talazoparib plus enzalutamide arm of the original clinical trial.

Overall, 48.0% of patients experienced grade ≥3 anemia, 7.8% experienced grade ≥3 thrombocytopenia, and 19.7% experienced grade ≥3 neutropenia. An exposure-response evaluation found that a higher average talazoparib concentration was associated with an increased risk of severe anemia and thrombocytopenia, and a higher log talazoparib concentration was associated with a greater risk of severe neutropenia. Lower baseline hemoglobin was associated with a higher risk of all hematological AEs, and lower baseline body weight was associated with greater risk of grade ≥3 anemia and neutropenia. Lower baseline absolute neutrophil count was also associated with increased risk of grade ≥3 neutropenia.

“These findings support talazoparib dose modifications (dose interruption or reduction) as an effective approach for management of AEs with talazoparib plus enzalutamide combination therapy for patients with mCRPC,” the authors concluded.

Reference

Azad AA, Wang Y, Hadigol M, et al. Exposure-safety analyses of talazoparib in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer in TALAPRO-2 trial. Poster. Presented at the Hematology/Oncology Pharmacy Association Annual Conference 2024; April 3-6, 2024; Tampa, Florida.