Using CHFR expression to predict response and survival after first line treatment with carboplatin-paclitaxel in NSCLC.

Abstract

10625 Background: The identification of resistance mechanisms for conventional chemotherapy in lung cancer is of fundamental importance not only for personalization of chemotherapy but also for the subsequent development of novel targeted approaches to overcome this resistance. Currently, there is no clinically validated test for the prediction of response to tubulin-targeted agents in NSCLC. Our previous preclinical work identified Checkpoint with Forkhead and Ringfinger domain” (CHFR) as a predictor of taxane cytotoxicity in in vitro models. The current work assessed the translational significance of this finding in a cohort of US veterans treated at a single-institution. Methods: We studied a cohort of patients with advanced NSCLC treated with taxane-containing frontline regimens at the Atlanta VA Medical Center between 2000 and 2009. Archived paraffin-embedded tissue was retrieved and stained for CHFR expression using standard immunohistochemical techniques. Level of protein expression was assessed by light microscopy and scored for intensity of CHFR staining. Intensity of staining was correlated with clinical outcome including objective response and median overall survival using Chi-Square test and Cox proportional models. Results: We analyzed tumor samples from 45 eligible patients with median age 62.6 years, M/F (44/1). In this cohort, high expression of CHFR is strongly associated with adverse outcomes: the risk for progressive disease (PD) after first-line chemotherapy with carboplatin-paclitaxel was 54% in patients with CHFR-high vs. only 18% in those with CHFR-low tumors (HR 3.1; 95% CI 1.09-9.04; p=0.02). Median overall survival was strongly correlated with response to first-line therapy (clinical benefit: 9.24 months; PD: 4.7 months; p<0.001) and with CHFR expression status (CHFR low: 10 months; CHFR high: 5.6 months; p =0.01). Conclusions: CHFR expression is a novel predictive marker of response and overall survival in NSCLC patients treated with taxane-containing chemotherapy.