1266P - Retrospective study of clinicopathologic factors associated with ALK rearrangement and survival outcome in Chinese patients (pts) with NSCLC

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Xuchao Zhang
Authors X. Zhang1, C. Blanckmeister2, Y. Cheng3, D. Wu4, J. Yang5, H. Tian5, J. Chen6, Z. Xie5, H. Yan5, Y. Wu7
  • 1Lung Cancer Institute, Guangdong Lung Cancer Institute,, Guangdong/CN
  • 2Ny Ny 10017, Pfizer, New York/US
  • 3Oncology, Jiling Province Tumor Hospital, Jilin/CN
  • 4Huguang Street 1018,, Jilin Provincial Cancer Hospital, Jilin Province,/CN
  • 5Guangdong General Hospital, Guangdong Academy Of Medical Sciences, Guangdong Lung Cancer Institute,, Guangdong/CN
  • 636/f, Citic Square, 1168 Nan Jing Road( W),, Pfizer China Medical Affairs, Shanghai 200041,/CN
  • 7Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN



We tested 400 NSCLC pts for ALK, EGFR and KRAS status and correlated clinical factors with ALK status and overall survival (OS).


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.


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.


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.


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.