Predictors of outcome for pemetrexed (Pem) in metastatic NSCLC (mNSCLC)

e19025 Background: Pemetrexed (Pem) is the first agent showing different efficacy based on histology in the treatment (tx) of NSCLC. Our goal was to identify outcome predictors in patients (pts) with metastatic NSCLC (mNSCLC) treated with pem. Methods: Retrospective data of pts with mNSCLC who received pem were analyzed. Variables included demographics, ECOG performance status (PS), disease sites, pre/post-pem tx, and toxicities. Clinical benefit defined as complete response (CR), partial response (PR), and stable disease (SD) >6 months, progression-free survival (PFS), and overall survival (OS) were analyzed using logistic regression and Cox proportional hazards model. Results: 240 pts were included. 55% male, 84% smokers. 68% adenocarcinomas, 10% squamous/adenosquamous carcinomas. Median age 64 years (range 34-84). Pem was given for a median of 4 cycles (range 1-73), as 1st line in 20% and 2nd line in 50%, given as a single agent in 69%. The most common toxicities were constitutional (50%) and GI related (29%). 31% of pts achieved CR (n=4) or PR, 33% progressed, 36% had SD. Front-line pem use (p=.0003), adenocarcinoma histology (p=.05), and non-pulmonic metastatic sites ≤2 (p=.01) were independent predictors of clinical benefit, with response rate of 71% for pts with all three features, compared to only 7% for pts with none of these features. Multivariable analysis of survival data revealed ECOG PS >1, non-pulmonic metastatic sites>2, and squamous/poorly differentiated histology predicted poor PFS and OS. In addition, interval from diagnosis to start of pem 2 non-pulmonic metastatic sites, squamous/poorly differentiated histology predict poor PFS and OS. An analysis of biomarkers is ongoing.