Prognostic Factors in Metastatic Melanoma: A Pooled Analysis of Eastern Cooperative Oncology Group Trials

Abstract

PURPOSE: To identify factors that are prognostic for survival in patients with metastatic melanoma treated in eight Eastern Cooperative Oncology Group (ECOG) trials conducted over the past 25 years. METHODS: We identified common, significant patient characteristics collected at baseline on 1,362 eligible patients for inclusion in a pooled analysis. Proportional hazards models were used to examine simultaneously the effects of multiple covariates on survival. RESULTS: Median survival was 6.4 months (95% confidence interval, 6.1 to 6.9 months.) Factors conferring the greatest increased risk of death included number of metastatic sites (relative risk [RR] = 1.12), ECOG performance status of 1 or more (RR = 1.49), or metastatic disease in the gastrointestinal (GI) tract (RR = 1.49), liver (RR = 1.44), pleura (RR = 1.35), or lung (RR = 1.19). Prior immunotherapy (RR = 0.84) and female sex (RR = 0.87) were associated with prolonged survival. Although only 12% of patients responded to protocol treatment, landmark analysis showed this to be a significant prognostic factor (RR = 0.57). A model based on three recent studies in which baseline values for alkaline phosphatase, lactate dehydrogenase (LDH), and platelets were available identified an increased number of sites of metastasis (RR = 1.30), abnormal LDH (RR = 1.89), abnormal alkaline phosphatase (RR = 1.76), abnormal platelets (RR = 1.63), and GI metastases (RR = 1.66) as prognostic for poorer survival. Response to treatment, when examined by landmark analysis of studies with laboratory parameters, was associated with decreased risk of death (RR = 0.47). CONCLUSION: This study demonstrates the importance and utility of laboratory parameters as prognostic factors for survival and confirmed the deleterious effects of multiple metastatic sites. Prior immunotherapy and female sex were associated with improved prognosis. Prognostic factors identified in this analysis are consistent with the findings of prior published studies and argue for the adoption of laboratory findings in the staging systems that are used for entry and stratification of clinical trials in the future.