(ChemotherapyAdvisor) – Erlotinib combined with entinostat does not improve survival outcomes of patients with non-small cell lung cancer, according to a study published by Syndax Pharmaceuticals, Waltham, MA. The study, entitled “Randomized Phase II Trial of Erlotinib with and without Entinostat in Patients with Advanced Non–Small-Cell Lung Cancer Who Progressed on Prior Chemotherapy,” will be published in the May issue of Journal of Clinical Oncology and is currently available online.
According to the study’s authors, histone deacetylase inhibitors (HDACis) have been shown to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients met several inclusion criteria for this Phase 2 study: diagnosis with stage 3B/4 non–small-cell lung cancer, no prior treatment with EGFR-TKIs, and performance status ≤2. Patients were randomized to one of two treatment groups: erlotinib (150mg; administered on days 1–28) plus entinostat (10mg; administered orally on days 1–15, every 28 days; [EE]) or erlotinib plus placebo (EP). Dosing continued until the primary end point — 4-month progression-free survival (PFS) rate — was reached. Additional end points, including 6-month PFS rate, PFS, and overall survival (OS) were also evaluated.
Enrollees totaled 131 patients (EE, 67; EP, 65). “The 4-month PFS rate was comparable for both groups (EE, 18% vs. EP, 20%; P=.7). In the subset of patients with high E-cadherin levels, OS was longer in the EE group compared with the EP group (9.4 vs. 5.4 months; hazard ratio, 0.35; 95% CI, 0.13–0.92; P=.03) with a corresponding trend toward increased PFS. The most common adverse events in both groups were rash, fatigue, diarrhea, and nausea,” the investigators reported.
The investigators concluded: “Erlotinib combined with entinostat did not improve the outcomes of patients in the overall study population when compared with erlotinib monotherapy.”