Survival outcome segregated by KRAS mutation status in newly diagnosed stage IV non-small cell lung cancer (NSCLC) patients (pts) treated with first-line chemotherapy.

Abstract

7595 Background: KRAS mutations (MT) form a distinct subset of NSCLC, generally considered to have poor prognosis. Although KRAS MT is a well-establised prognostic and predictive marker in colorectal cancer, its role in NSCLC remains ambiguous. Pts with KRAS MT NSCLC do not respond well to epidermal growth factor receptor (EGFR) directed tyrosine kinase inhibitor therapy, but little is known about the ability of KRAS MT to predict outcome after first-line chemotherapy in newly diagnosed advanced or recurrent NSCLC. Methods: We analyzed outcomes of consecutive pts with newly identified Stage IV non- squamous NSCLC treated at University of Pennsylvania (Penn) between 05/2008 and 7/2010 and then compared survival based on KRAS status [MT vs wild type (WT)] using chi square, Kaplan-Meier methods, and Cox regression models. Results: Of 106 consecutive new pts with Stage IV non squamous NSCLC treated at Penn, 49 (46%) underwent molecular analysis for KRAS MT. Fifteen (34%) were KRAS MT. Of 34 KRAS WT pts, 6 were positive for EGFR MT. The median age of all 49 pts was 61 years; 83% were Caucasian, 45% male and 60% had a >10 pack year smoking history. Median duration of follow up is 16.4 mos. Majority of pts (92%) had adenocarcinoma histology. Most pts (88%) had ECOG PS 0-1 at presentation. Forty three pts received first line platinum-based combination chemotherapy (platinum and pemetrexed in 31 pts). KRAS MT was associated with smoking (p=0.04), but not with gender or age. Overall survival (OS) of pts with KRAS MT was similar to KRAS WT pts [median OS 15.6 vs. 19.0 mos; HR 1.24 (95% CI 0.57-2.67)]. Univariate analyses demonstrated superior OS among women compared to men (HR 0.40, 95% CI 0.20-0.85) in the entire pt cohort. Conclusions: In our population of stage IV non squamous NSCLC, pts with KRAS MT had similar OS to those with KRAS WT tumors. OS was slightly higher in KRAS WT pts, but this may have been confounded by the inclusion of 6 EGFR MT pts in this cohort. The potential prognostic or predictive role of KRAS MT in NSCLC pts undergoing chemotherapy requires further prospective study.