A vaccine, under development in Cuba for more than 2 decades, has shown potential to improve survival in patients with advanced non-small cell lung cancer.
A vaccine, under development in Cuba for more than 2 decades, has shown potential to improve survival in patients with advanced non-small cell lung cancer (NSCLC) by preventing the interaction between epidermal growth factor (EGF) and the epidermal growth factor receptor (EGFR).
Clinical Cancer Research
In a paper published in , authors describe the vaccine—named CIMAvax-EGF—as a human recombinant EGF, conjugated to a P64K Neisseria meningitides recombinant protein. The vaccine is designed to sequester EGF and prevent its interaction with EGFR, which is overexpressed in a majority of NSCLC tumors, thereby preventing cancer cell proliferation.
The phase 3 efficacy, safety, and immunogenicity trial of CIMAvax-EGF recruited 405 patients with stage IIIB/IV NSCLC, 4 to 6 weeks after first-line, platinum-based chemotherapy. Patients were randomly assigned to the vaccine group, which received the vaccine along with best supportive care, or the control group, which was provided the best supportive care. Every 2 weeks during the induction period, 4 doses of the vaccine were administered, followed by a monthly dose.
Following a baseline assessment, a physical exam and a clinical test was performed every 4 weeks. Additionally, chest radiography, computed tomography scan, and abdominal ultrasound were performed at baseline and every 3 months to assess clinical response according to Response Evaluation Criteria In Solid Tumors or RECIST. Patients were also monitored for toxicity at every visit, according to the NCI Common Toxicity Criteria, and vaccination was halted under circumstances of unmanageable toxicity, severe worsening of the patient’s general conditions, or if the patient withdrew voluntarily.
This phase 3 study claims that long-term vaccination was found safe in patients, and grade 1 or 2 injection-site pain, fever, vomiting, and headache were the most commonly documented adverse reactions. Confirming the proof of concept, the vaccine reduced serum EGF levels. Among patients who received at least 1 dose of the CIMAvax-EGF vaccine, classified as the safety population, survival benefit was non-significant when analyzed using the log-rank test (hazard ratio [HR], 0.82; 95% CI, 0.661-1.03; = .100), the authors report. In the safety cohort, patients treated with the vaccine had a median survival time (MST) of 10.83 months, compared with 8.86 months in the control arm. However, a weighted log-rank analysis confirmed the results as significant ( = .04). the 5-year survival rate was 14.4% in the vaccinated patients and 7.9% among controls.
In the pre-protocol group, 4 doses of the trial vaccine resulted in a significant 3-month improvement in survival (HR, 0.77; = .036). MST in the vaccine arm was 12.43 months (95% CI, 10.42-14.45) compared with 9.43 months (95% CI, 7.53-11.33) in the control arm. The 5-year survival rate was 16.62% in the vaccinated cohort and 6.2% in the control group.
When trying to correlate the survival results with EGF expression, the authors found that high basal EGF expression may be an indicator of poor prognosis in NSCLC patients.
The vaccine, approved for use in adults with advanced NSCLC in Cuba in 2008, will also be tested in the United States. The Roswell Park Cancer Institute in New York, has agreed to collaborate with Cuba’s Center for Molecular Immunology (which developed the vaccine) to gain FDA approval for CIMAvax-EGF. The objective of the clinical trials at Roswell Park will be to validate these observations, to measure circulating EGFR and antibody response, and to “independently assess if we see similar outcomes in our own population,” Grace Dy, MD, a thoracic medical oncologist at Roswell Park, who’ll be leading the trial, told Medscape. The trial will evaluate the vaccine in combination with the immune checkpoint inhibitor, nivolumab.
Clin Cancer Res
Rodriguez PC, Popa X, Martínez O, et al. 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. . 2016;22(15):3782-3790. doi: 10.1158/1078-0432.CCR-15-0855.