Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: Overall results of a randomized trial of the Southwest Oncology Group

Purpose : Patients with clinically negative nodes constitute over 85% of new melanoma cases. There is no adjuvant therapy for intermediate-thickness, nodenegative melanoma patients. Patients and Methods: The Southwest Oncology Group conducted a randomized phase III trial of an allogeneic melanoma vaccine for 2 years versus observation in patients with intermediate-thickness (1.5 to 4.0 mm or Clark's level IV if thickness unknown), clinically or pathologically node-negative melanoma (T3N0M0). Results: Six hundred eighty-nine patients were accrued over 4.5 years; 89 patients (13%) were ineligible. Surgical node staging was performed in 24%, the remainder were clinical NO. Thirteen eligible patients refused assigned treatment: seven an the observation arm and six on the vaccine arm. Most vaccine patients experienced mild to moderate local toxicity, but 26 (9%) experienced grade 3 toxicity. After a median follow-up of 5.6 years, there were 107 events (tumor recurrences or deaths) among the 300 eligible patients randomized to vaccine compared with 114 among the 300 eligible patients randomized to observation (hazard ratio, 0.92; Cox-adjusted P-2 = 0.5 1). There was no difference in vaccine efficacy among patients with tumors less than or equal to. 3 mm or > 3 mm. Conclusion: This represents one of the largest randomized, controlled trials of adjuvant vaccine therapy in human cancer reported to date. Compliance with randomization was excellent, with only 2% refusing assigned therapy. There is no evidence of improved disease-free survival among patients randomized to receive vaccine, although the power to detect a small but clinically significant difference was low. Future investigations of adjuvant vaccine approaches for patients with intermediate-thickness melanoma should involve larger numbers of patients and ideally should include sentinel node biopsy staging. (C) 2002 by American Society of Clinical Oncology.