Active specific immunotherapy with a polyvalent cancer vaccine prolongs survival in AJCC stage IV melanoma

Abstract

2543 Background: The treatment of AJCC stage IV melanoma is inadequate; in a recent meta-analysis, median and 5-year survivals were 8.1 months and 2.3%. In phase II trials, we have evaluated the activity of active specific immunotherapy with a polyvalent therapeutic cancer vaccine (Canvaxin) and other immune adjuvants against stage IV melanoma. We compared the survival of vaccine-treated patients with the survival of comparable surgical and nonsurgical patients receiving nonvaccine therapies. Methods: Our study groups included all AJCC stage IV patients (N=1856) entered into our prospective database of 11,000 patients between 1/1/86 and 1/1/2001. Survival curves were estimated by Kaplan-Meier method, and statistical difference analyzed by log rank test and Cox regression according to the new AJCC staging system of Mla, Mlb and Mlc. Results: Although complete regression of evaluable disease was rare among vaccine patients, disease stabilization was common. Survival from initial stage IV diagnosis was prolonged almost twofold for the entire group of vaccine patients and for all vaccine-treated M1 subgroups (p = 0.001 - 0.05) except Mla (Table); 1-, 2-, 3- and 5-year survival rates were also significantly enhanced (p = 0.001). Toxicity of vaccine therapy was minimal: transient grade 1 or 2 fever, headaches, malaise and ulcerations at the injection sites. Skin-test and antibody responses to vaccine antigens were associated with enhanced survival. Conclusions: When compared with other postsurgical adjuvants and nonsurgical therapies, polyvalent vaccine immunotherapy significantly enhanced the survival of patients with resectable and nonresectable stage IV melanoma. This is the largest vaccine study yet reported, and the survivals are the longest yet observed in stage IV melanoma. These findings deserve further study in a multicenter randomized trial, which is currently underway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CancerVax Corp. CancerVax Corp. CancerVax Corp.