An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites

Abstract

8508 Background: Active specific immunotherapy with BCG and an allogeneic, melanoma cell vaccine can induce antibody and T-lymphocyte immune responses to numerous antigens expressed by melanoma cells. This study compared overall and disease-free survival in patients receiving BCG plus placebo versus BCG plus MCV. Methods: Between June 1998 and November 2005, 1,656 patients without evidence of residual disease after resection of stage III (n = 1,160) or stage IV (n = 496) melanoma were randomly assigned to the two treatment arms (1:1). BCG was given as an immunologic adjuvant for the first two injections of both MCV and placebo, which thereafter were administered by intradermal injection every two weeks for the next three injections, every month for the remainder of the first year, every two months for the second year and every three months for years three, four and five. Results: Based on the recommendation of the independent Data and Safety Monitoring Board (DSMB), both studies were terminated after the interim analysis. The recommendation was based on a low probability of demonstrating significant improvement in survival of the BCG plus MCV arm if the study had continued to completion of follow-up and final analysis. Conclusions: This is the largest multicenter clinical trial of postoperative adjuvant immunotherapy after resection of melanoma metastatic to regional lymph nodes or distant sites. It is a landmark study not only because it represents the first randomized multicenter trial to use surgical resection as initial therapy for stage IV melanoma patients with up to five metastatic sites, but also because its results demonstrate excellent survival for the entire study population with 42.3% of stage IV and 63.4% of stage III patients projected to be alive at five years. Updated data for survival and immunologic endpoints which show a significant correlation between immune responses and survival will be provided at the meeting. [Table: see text]