Talazoparib for Metastatic Castration-Resistant Prostate Cancer

Patient Selection and Treatment

The National Comprehensive Cancer Network strongly recommends talazoparib plus enzalutamide for first-line treatment of metastatic castration-resistant prostate cancer in patients with HRR gene mutations who have not received prior novel hormone therapy or docetaxel in the CRPC setting 1, 2
The American College of Physicians and the National Comprehensive Cancer Network suggest that patients with HRR gene mutations who received prior docetaxel in the castration-sensitive setting but no prior novel hormone therapy in CRPC may be considered for talazoparib plus enzalutamide 1, 2
The benefit of talazoparib varies dramatically based on the specific HRR mutation, with BRCA1/2 mutations showing a 77% reduction in radiographic progression or death 1, 2, 3

Talazoparib plus enzalutamide results in a 34% reduction in progression risk for non-BRCA HRR mutations, although this is not statistically significant 1, 2, 3
The combination of talazoparib and enzalutamide carries significant hematologic toxicity, with grade ≥3 anemia occurring in 46% of patients 1
Dose interruptions and reductions are common, with 75% and 56% of patients requiring them, respectively 1, 2, 3

The National Comprehensive Cancer Network recommends that all patients with metastatic castration-resistant prostate cancer undergo both germline and somatic genomic testing with next-generation sequencing technologies before treatment initiation 6
Complete blood count monitoring is mandatory throughout treatment, and type and screen availability with transfusion support readiness is required 4, 5

The National Comprehensive Cancer Network also recommends olaparib plus abiraterone and niraparib plus abiraterone for BRCA1/2 mutations, with the choice between these combinations depending on specific androgen receptor inhibitor preference, toxicity profiles, and mutation type 1, 2, 3, 4, 5