Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF. There was a direct correlation between antibody response and survival. There was a direct correlation between decrease in serum EGF and survival. In patients younger than 60 years, vaccination was associated with increased survival.

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KEY WORDSepidermal growth factor, epidermal growth factor receptor, EGF vaccine, non-small Treatment of NSCLC Patients with an EGF-Based Cancer VaccineReport of a Phase I Trial ABSTRACT Epidermal Growth Factor (EGF) promotes tumor cell proliferation and survival upon binding to its receptor. We have developed a new active specific immunotherapy based on EGF deprivation. In the present paper, we show the results of a Phase I trial in 43 patients with advanced non-small cell lung cancer (NSCLC) who received the EGF vaccine. Patients who had already received first line therapy were randomized to receive a single or double dose of the EGF vaccine, weekly for four weeks and monthly thereafter. No significant toxicity was seen after vaccination. Adverse events consisted primarily of fever, chills, nausea, vomiting and flushing. Fifteen patients (39%) developed a good antibody response (GAR) against EGF. The geometric mean of the antibody titer was higher in the double dose group. EGF concentration was quantified in serum. An inverse correlation between anti-EGF antibody titers and EGF concentration was seen after immunization. Vaccinated patients achieved median survival times of 8.23 months from randomization. Patients who received the double dose of treatment showed a trend toward increased survival in comparison with patients who received the single dose. GAR and patients in whom the serum EGF decreased below the 168 pg/ml cut-off point had a significantly better survival when compared to poor responders or patients in which the EGF levels were not considerably reduced. Our results confirm the immunogenicity of the EGF vaccine in the treatment of patients with advanced stage NSCLC. Antibody titers and serum EGF levels appear to correlate with patient survival.

Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial tumors and its role in the development of non-small-cell lung cancer (NSCLC) is widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by recombinant EGF conjugated to a carrier protein and emulsified in Montanide ISA51. Vaccination induces antibodies against self-EGF that block EGF-EGFR interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted to optimize vaccine formulation and schedule. Then, two randomized studies were completed in advanced NSCLC, where CIMAvax-EGF was administered after chemotherapy, as 'switch maintenance'. The vaccine was very well tolerated and the most frequent adverse events consisted of grade 1/2 injection site reactions, fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF concentration was reduced after vaccination. Subjects receiving a minimum of 4 vaccine doses had a significant survival advantage. NSCLC patients with high EGF concentration at baseline had the largest benefit, comparable with best maintenance therapies.

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