A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients

Purpose:Epidermal Growth Factor Receptor (EGFR) is a well validated target for Non-Small-Cell-Lung-Cancer (NSCLC) patients. CIMAvax-EGF is a therapeutic cancer vaccine composed by human-recombinant EGF conjugated to a carrier protein and Montanide ISA51, as adjuvant. The vaccine is intended to induce antibodies against self EGF that block EGF-EGFR interaction. Experimental Design:To evaluate overall survival, safety, immunogenicity and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in advanced NSCLC patients. Four to 6 weeks after first-line chemotherapy, 405 stage IIIB/IV NSCLC patients were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. Results:arm. These differences were not significant according the standard log-rank (HR 0.82; p=0.100) but according a weighted log-rank (p=0.04), that was applied once the non-proportionality of the hazard ratio was verified. Survival benefit was significant (HR 0.77; p=0.036) in the per-protocol setting (patients receiving at least 4 vaccine doses): MST was 12.43 months for the vaccine arm vs. 9.43 months for the control arm. MST was larger (14.66 months) for vaccinated patients with high EGF concentration at baseline. Conclusions:Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit.