Therapeutic Vaccination with Epidermal Growth Factor (EGF) in Advanced Lung Cancer: Analysis of Pooled Data from Three Clinical Trials

Abstract

KEy wordscancer vaccine, epidermal growth factor, non-small cell lung cancer AbbrEViATioNs AbsTrACTWe have undertaken the analysis of pooled data from three pilot clinical trials of vaccination with Epidermal Growth Factor (EGF) in patients with advanced non small cell lung cancer (NSCLC), addressing particularly the issue of the relationship between immunization and survival. Eighty-three patients with advanced disease were included in three pilot clinical trials and vaccinated with the EGF Vaccine. The trials were designed to evaluate the immunogenicity and safety of the vaccine using different adjuvants, cyclophosphamide pretreatment or not, and different dosage levels of the vaccine. The vaccine elicited specific anti-EGF antibody titers in 83% of subjects, and 49% developed a good anti-EGF antibody response. The adjuvant, the vaccine dose, and cyclophosphamide pretreatment significantly influenced immunogenicity. Patients that seroconverted survived significantly longer than patients who did not. Good antibody responders survived significantly longer than poor responders. Pooled results from these trials confirm that vaccination with EGF is safe and immunogenic in advanced NSCLC patients. The association between good antibody responses and survival consistently appeared in every single trial independently of the specific trial designs. Although these were small pilot nonrandomized clinical trials not intended to confirm therapeutic effect, the survival of the pooled patient population was statistically greater compared with 163 control patients receiving standard treatment.

CIMAvax EGF vaccine for stage IIIb/IV non-small cell lung carcinoma

“…Pooled data from three phase I/II randomized trials (n = 83, all of whom had had at least one line of conventional treatment) showed that, on average, vaccinated patients had a mean survival time of almost double that of concurrent unvaccinated controls (9.13 vs. 4.85 mo, p < 0.02). 4 A larger scale Phase II randomized controlled trial (n = 80) produced similar results. 5 It added that vaccinated patients under the age of 60 had an especially improved median survival time over control subjects (11.57 vs. 5.33 mo, p < 0.02).…”

“…Ongoing vaccination is necessary to boost antibody titers back to peak levels. 4 Therefore it is interesting that her disease has not shown progression after her last injection some 28 mo previously. Her age may be a contributing factor-54 y old at time of vaccine commencement.…”

“…4,5 Those whose antibody titers rise above this case report documents the use of the CIMavax epidermal Growth Factor vaccine regimen in a 54 year old female with stage IIIb non-small cell lung carcinoma. even after 48 mo since diagnosis her eCoG performance remains at zero.…”

“…80% of those given cyclophosphamide before the CIMAvax course will demonstrate some anti-EGF activity. 4 Effectiveness is further enhanced if the vaccine is injected over multiple sites as our case was. 9 Doing so may involve more lymph node regions.…”

“…Trials have shown that the addition of P64K and adjuvant-Montanide ISA 51 (Seppic)-increase seroconversion rates while being low in immunogenicity themselves. 4,[13][14][15] Documented side effects are mild. These include tremors, headache, constitutional symptoms and arthralgia.…”