Association between triglyceride (TG) levels, other clinical characteristics, and outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with erlotinib and bexarotene

Abstract

8101 Background: Studies of the nonclassical retinoid bexarotene (B) alone or in combination with chemotherapy have revealed improved survival for a subset of NSCLC patients (pts) who developed hypertrigyceridemia despite treatment with antilipid agents. It is not known if a similar association exists when B is combined with a targeted agent. We have completed 2 trials of erlotinib (E), and B, in pts with advanced NSCLC showing minimal toxicities and evidence of clinical activity. In both trials atorvastatin was begun only after elevated TG were detected. This approach differed from other studies where statin therapy was initiated concurrently with B. Methods: E 150 mg and B 400 mg/m2 were administered daily orally to pts with stage IV NSCLC, mostly as third line or higher. Atorvastatin 20 mg was started for elevated fasting TG. The dose was increased to 40 mg if hypertriglyceridemia persisted, followed by the addition of fenofibrate and/or dose reductions of B to 300 mg/m2. TG levels assessed in the first 4 weeks were correlated with overall survival. The appearance of skin rash was documented. Results: Sixty-one pts with stage IV NSCLC were enrolled, 54% women and 72% with adenocarcinoma, 15% never smokers, 20% current smokers, 15% had prior anti-EGFR therapy. Median survival time (MST) was 22 (1–274) wks (intent-to-treat). For pts with elevated TG, the MST was 24 (1–274) wks, while for pts with normal TG the MST was 21 (4–72). There was a statistically significant correlation between TG levels and survival, Spearman's correlation coefficient 0.48, p=0.0003. We will present the analysis of the association between outcomes and other clinical characteristics. Conclusions: Development of hypertriglyceridemia in the first 4 weeks of therapy with E and B in the absence of antilipid treatment is associated with increased overall survival. These findings implicate clinical benefit of dual targeting of EGFR and cyclin D1 especially in a subset of NSCLC pts with elevated TG early in therapy. Further work to identify the molecular basis for this association is needed to allow selection of pts more likely to benefit from this combined therapy. [Table: see text]