High Levels of Serum EGF Concentration Predict Response to Cimavax-EGF Treatment in Advanced NSCLC

Abstract

Inhibition of EGFR signalling has shown to be relevant for the treatment of some patients with NSCLC. CIMAvax-EGF is a therapeutic vaccine that induces an antibody response against circulating serum EGF. In a randomized Phase III trial, CIMAvax-EGF improved the overall survival of advanced NSCLC patients as compared to best supportive care, when administered as switch maintenance. Exploratory results suggested serum EGF concentration could function as prognostic and predictive biomarker. In this study, we aimed to further assess whether pre-treatment serum EGF level is a predictive biomarker of survival benefit in advanced NSCLC patients treated with CIMAvax-EGF. A pooled analysis of 2 blinded, randomized, controlled clinical trials of CIMAvax-EGF for NSCLC was done. Patients were assigned to one of two groups: biomarker positive (≥870 pg/mL) or biomarker negative (<870 pg/mL) based on pre-treatment serum EGF concentrations. Patients from each group received CIMAvax-EGF or best supportive care. The primary outcome was overall survival. In a pooled cohort of 229 patients, 120 were considered biomarker positive (BM+) and 109 considered biomarker negative (BM-). In the BM + population, HR for overall survival (CIMAvax-EGF vs BSC) was 0.44, p=0.001.A significant biomarker/treatment interaction was found (p=0.001). We conclude that a high pre-treatment serum EGF level is a predictive biomarker of survival benefit in advanced NSCLC patients treated with CIMAvax-EGF.