Introduction: Prostate cancer (PCa) is the second most common cancer diagnosis among men worldwide, with poor prognosis in its advanced stage. Treatment strategies have evolved, including the use of androgen receptor pathway inhibitors (ARPIs) and poly (ADP-ribose) polymerase inhibitors (PARPis).
Areas covered: This review evaluates the clinical efficacy, safety, and future potential of combining talazoparib, a potent PARPi, with enzalutamide, a strong androgen receptor (AR) antagonist. The combination of these two drugs was evaluated by the TALAPRO-2 trial, demonstrating significant improvement in radiographic progression-free survival (rPFS) in metastatic castration-resistant prostate cancer (mCRPC) patients, particularly those with Homologous Recombination Repair (HRR) gene mutations such as BRCA1/2.
Expert opinion: Emerging biomarkers like TMPRSS2-ERG and RB1 gene mutations have been recently reported as potential predictors of clinical outcome in the TALAPRO-2 all-comers population. Genomic markers for homologous recombination deficiency (HRD) are other potential drivers of response to PARPi/ARPI combination. Further investigation is needed to refine treatment strategies, including targeting non-HRR mutations, and to expand the role of this combination therapy in earlier stages of prostate cancer.
Keywords: HRD; HRR; PARP inhibitor; RB1; TMPRSS2-ERG; enzalutamide; mCRPC; talazoparib.