Dr Piulats on Predictive Biomarkers for Treatment With Talazoparib/Enzalutamide in mCRPC

Josep Maria Piulats Rodriguez, MD, PhD, chair, Uveal Melanoma, the Spanish Melanoma Group, medical oncologist, Institut Català d’Oncologia–Bellvitge Institute for Biomedical Research, discusses findings from a post-hoc analysis evaluating predictive biomarkers for treatment with talazoparib (Verzenio) plus enzalutamide (Xtandi) vs placebo plus enzalutamide as first-line treatment in patients with metastatic castration-resistant prostate cancer.

These findings were shared at the 2024 AACR Annual Meeting. In this analysis, investigators identified various genes, 1 of which was excluded from the analysis due to its apparent dependence on the other genes: TMPRSS2-ERG and RB1, Piulats begins. Since all patients with ERG fusions also had TMPRSS2 fusions, investigators grouped these genes together, Piulats states.

Findings revealed significant benefits with talazoparib plus enzalutamide for the TMPRSS2-ERG fusion population, particularly in terms of progression-free survival (PFS). Patients with TMPRSS2-ERG fusions who were treated with placebo plus enzalutamide exhibited a median PFS of 11 months, whereas those receiving talazoparib plus enzalutamide demonstrated an approximate 25.9-month median PFS, Piulats reports; however, because this was a post-hoc analysis, further studies are required to validate these results.

RB1 is a gene known for its role in driving plasticity toward more aggressive prostate cancer subtypes that are resistant to castration, indicating a poor prognosis for patients harboring RB1 mutations, Piulats expands. However, the study did not conclusively determine whether this effect directly stems from RB1 loss or is associated with other factors, given its proximity to BRCA2, according to Piulats. Further investigations are necessary to elucidate this distinction, Piulats explains. Although only 1 patient with an RB1 mutation also had a BRCA1 mutation, both genes are susceptible to loss, potentially influencing the study outcomes, Piulats emphasizes. Notably, since this study used circulating tumor DNA (ctDNA) assays, investigators acknowledged the limitations of liquid-based testing compared with tissue-based testing, he says. Future analyses will incorporate tissue-based results for a comprehensive understanding of these findings, Piulats explains.

Based on feedback received at the 2024 AACR Annual Meeting, investigators plan to merge both the ctDNA and tissue-based assay datasets to gain further insights into these findings, Piulats concludes.