Lung cancer in never-smokers from the Princess Margaret Cancer Centre.

8099 Background: Lung cancer in never smokers accounts for ~15-20% of cases, and globally is a growing clinical problem. Methods: We identified 570 never-smokers with lung cancer diagnosed from 1988-2013 at the Princess Margaret Cancer Centre. Clinical and demographic data were retrieved from the electronic patient record with the aim of characterizing the epidemiology, demographics, pathology, molecular profile, treatment, and survival in these patients. Results: There were 409 females (72%) and 161 males (28%), median age 62.1 years (18– 94), 46% Caucasian, 34% Asian, 6% Black, 4% South Asian, 4 % Filipino, 6% Other/Unknown. Environmental tobacco exposure was identified in only 17%. A history of prior malignancy was present in 89 (14.2%) patients (1 cancer 81; multiple cancers 8 patients). Most patients (87.3%) had adenocarcinoma and most presented in stage IV - 54.9%, followed by I - 26%, III - 12.8% and II - 6.3%. In stage IV patients, 88% were ECOG PS 0-1. Among 310 patients with molecular results to date, the mutation rate was 71% (EGFR mutation [mut] 76%, ALK 10%, KRAS 4%, HER2 1.4% BRAF 0.5%, other 1.8%, multiple mut 6.3%. Brain metastases at presentation occurred in 18.4% stage IV patients (77/419): 67% (52/77) with EGFR mut vs 22% (17/77) with EGFR WT vs 10% (8/77) with other mut (P=0.0023). Median overall survival (OS) of EGFR mut patients vs EGFR WT with brain metastases at presentation was 57 vs 16 mo (P=0.031). Stage IV patients with EGFR and ALK mut received targeted treatment in 88% (121/138) and 89% (16/18) cases, respectively, with 65% (92/138, 66% for EGFR and 14/18, 82% for ALK) staying on TKI >6 months. Overall, 68% (285/419) of patients received 1-3 lines of systemic therapy (range 0-8 lines). Median OS was 47 mos. Median OS for patients with known vs unknown mutation status was 59 mo vs 34 (P<0.001). Early stage (P<0.0001), PS 0-1 (P<0.0001), presence of EGFR (P=0.003) or ALK mut (P=0.035) were associated with longer survival, but not Asian ethnicity (P=0.6) or female sex (P=0.1). Conclusions: Lung cancer in never-smokers represents a distinct clinical and molecular entity characterized by a high incidence of targetable mutations and long survival. Updated molecular profiling results will be presented for the entire cohort.

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