Components of metabolic syndrome correlate with longer survival in NSCLC in bexarotene-treated patients with high hypertriglyceridemia in SPIRIT I and II trials: A retrospective analysis

Abstract

7137 Background: Bexarotene activates RXR receptors regulating cell proliferation, differentiation, apoptosis and many aspects of lipid metabolism. Both SPIRIT I and II trials (ASCO 2005) showed that a large (36%) subgroup of bexarotene-treated patients showing high sensitivity to hypertriglyceridemia had a significantly longer survival in both studies. This subgroup included males, smokers, stage IV and weight loss, factors associated with poorer survival. A recent study in retinoid-treated patients revealed those developing high hypertriglyceridemia, as well as their parents, have a familial predisposition to hyperlipidemia and the metabolic syndrome (Ann Intern Med, 2002, 136:582). We evaluated baseline and in-treatment patient characteristics in relation to triglyceride responses and overall survival after bexarotene treatment to further extend that observation to NSCLC patients. Methods: A pooled analysis of 595 patients treated with bexarotene in SPIRIT I and II trials assessed factors related to metabolic syndrome (BMI, HDL, LDL and Total cholesterol [T-chol], T-chol/HDL ratio, triglycerides, glucose, blood pressure) at baseline and during treatment at the time of high-triglyceridemia. Individual and composite risk factor scores were evaluated by logistic and Cox-regression analysis in two subgroups, e.g., Responders (high trigs, long survival) and Non-responders (low trigs, shorter survival). Results: Among in-treatment risk factors, Responders (N = 215) had significantly higher (p < 0.0001) BMI, trigs, T-chol, T-chol/HDL ratio and lower HDL (p < 0.0001) than Non-responders (N = 380). A composite risk score (the sum of the individual in-treatment dichotomous risk scores) analysis also showed a significantly (p < 0.0001) higher score for metabolic risk factors in the Responder/longer survival subgroup. Hazard ratio analysis by Cox-regression showed a 13% survival benefit for each composite score increase. Conclusions: Baseline and in-treatment triglycerides and other key metabolic syndrome factors are important predictors and contributors to the beneficial survival impact of bexarotene in this important subgroup of NSCLC patients. [Table: see text]