1266P - Retrospective Study of Clinicopathologic Factors Associated with Alk Rearrangement and Survival Outcome in Chinese Patients (PTS) with NSCLC

Abstract

ABSTRACT Background We tested 400 NSCLC pts for ALK, EGFR and KRAS status and correlated clinical factors with ALK status and overall survival (OS). Methods ALK status was assessed with RACE-PCR, IHC and FISH; EGFR and KRAS status were assessed by direct DNA sequencing. OS was estimated by the Kaplan-Meier method. Results Consecutive, unselected cases from southern (n = 294) and northern (n = 106) China were tested; 31 (7.7%), 105 (26.2%) and 33 (8.2%) pts were ALK + , EGFR+ and KRAS + , respectively. ALK and EGFR aberrations were largely exclusive (P = 0.009); 2 cases were ALK + /EGFR+. ALK+ status was associated with female sex (P = 0.023), non/light-smoking (P = 0.001) and adenocarcinoma (P = 0.017), and was more prevalent in southern (9.2%; 27/294) than northern (3.8%; 4/106) pts. The ALK fusion partner was EML4 in all 31 cases; predominantly variants V1–3 (90.3%, 28/31). In 326 modeled pts, female sex (HR = 2.84; P = 0.022), wild type EGFR (HR = 15.87; P = 0.001), non/light-smoking (HR = 3.95; P = 0.021) and adenocarcinoma (HR = 4.12; P = 0.031) were associated with ALK+. In 187 cases evaluated by IHC and RACE-PCR, IHC sensitivity was 100% (19/19; [5 IHC + ; 10 IHC + +; 4 IHC + ++ ]) and specificity was 79.8% (134/168). All 19 ALK+ cases by RACE-PCR were also ALK+ by FISH. In the first 303 pts, there were no significant OS differences between ALK + , EGFR + , KRAS+ and triple-negative pts, between ALK+ and ALK– pts, or between ALK+ cases matched with non-TKI-treated controls balanced for disease stage, sex, histology and EGFR/KRAS status. In ALK+ pts, non/light-smoking status (P = 0.016) and prior surgery (P = 0.024) were associated with increased OS by log-rank test. In a Cox model, disease stage (P ≤ 0.001 for both stage I and II), and surgical treatment (P = 0.001) were prognostic for OS. Conclusion ALK fusion prevalence was 7.7% overall, and was higher in southern pts. ALK+ was associated with non/light-smoking, adenocarcinoma and female sex. ALK fusion variants were mostly V1–3, which may inform RT-PCR screening. IHC for ALK protein and FISH for ALK rearrangement may be useful for patient selection. ALK+ was not a favorable prognostic factor, although disease stage and smoking history may influence OS in ALK+ NSCLC. Disclosure C. Blanckmeister: Employment: Pfizer. Myself. Compensated. Stock ownership: Pfizer. Myself. J. Chen: Employment: Senior Medical Affairs Therapeutic Area Manager. Pfizer. Myself. Compensated. All other authors have declared no conflicts of interest.