E4697: Phase III cooperative group study of yeast-derived granulocyte macrophage colony-stimulating factor (GM-CSF) versus placebo as adjuvant treatment of patients with completely resected stage III-IV melanoma.

Abstract

8504 Background: Previous investigations suggested that GM-CSF might be effective in adjuvant therapy of melanoma. Methods: A prospective, randomized, placebo-controlled, phase III trial was conducted by ECOG, SWOG, and CALGB. Eligible patients had completely resected stages IIIB, IIIC, IV or mucosal melanoma. Patients were randomized to receive either GM-CSF 250 mcg or placebo SC daily for 14 consecutive days every 28 days for one year. The primary endpoint was overall survival (OS); with > 800 patients there is 80% power to detect a 33% increase in median survival from 40 months (mos) to 53.3 mos based on a log-rank test with 2-sided type 1 error of 0.05. A second endpoint was disease free survival (DFS), with 82.5% power to detect a 25% increase from 11 to 13.75 mos. The study called for unblinding after either full information (400 deaths) or 30 months after accrual was completed. The study was unblinded for time elapsed in April, 2009. Results were updated in September, 2009, with 330 deaths, and will be updated again in April, 2010. Results: Between December 29, 1999 and October 31, 2006 815 patients enrolled. As of this report 735 are confirmed eligible. Median OS is 59.8 mos (95% CI 45.3,−) for the placebo arm vs. 72.1 mos (CI 50.9,−) for the GM-CSF arm (p = 0.551, hazard ratio 0.935). Median DFS is 8.8 mos (CI 7.2,12.2) for placebo vs. 11.8 mos (CI 10.2,−) for GM-CSF (p = 0.034, hazard ratio 0.827). Toxicity was consistent with known effects of GM-CSF. Conclusions: Adjuvant GM-CSF improves DFS of patients with completely resected high-risk melanoma with minimal toxicity. OS improvement is less and does not achieve statistical significance. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA39229, CA32102, CA20319, CA31946, CA04326 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genzyme Genzyme