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H.S. Shim



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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-012 - Clinical and prognostic implication of ALK and ROS1 rearrangement in never smoker with surgically resected lung adenocarcinoma (ID 2232)

      09:30 - 09:30  |  Author(s): H.S. Shim

      • Abstract

      Background
      Rearrangements of oncogenic kinase proteins, anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1), were discovered as key oncogenic molecular drivers of lung adenocarcinoma recently. The aim of this study is to evaluate the prevalence and survival outcomes of ALK and ROS fusion in never smoker patients with surgically resected lung adenocarcinoma.

      Methods
      We analyzed consecutive stage IB to IIIA never smoker lung adenocarcinoma patients who underwent curative surgery in our institution. All resected tumors underwent comprehensive molecular profiling including EGFR mutation, KRAS mutation test, and fluorescence in situ hybridization (FISH) assay for ALK rearrangement. ROS1 rearrangement was evaluated by FISH assay in all triple-negative tumors (negative for EGFR, KRAS, and ALK).

      Results
      Of 162 never-smoker patients with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) patients had ALK and ROS1 rearrangement, respectively. Proportion of ALK or ROS fusion-positive (fusion-positive) patients was 26.0% (15 out of 73) among patients who are negative for EGFR and KRAS mutation. Fusion-positive patients tend to have a shorter disease free survival (DFS) than fusion negative patients, but without statistical significance (p= 0.124). However, multivariate analysis showed significantly poorer DFS of fusion-positive patients than fusion-negative patients with adjustment for T stage and lymph node metastasis (Hazard ratio 2.26; 95% Confidence interval, 1.19-4.30; p = 0.013). The 3-year DFS rate was 47.0% in fusion-negative patients and 32.7% in fusion–positive patients. Fusion-positive patients also showed poorer DFS in stage IB to IIB subgroup. (n=123, p= 0.046) Overall survival of patients was not different according to ALK or ROS fusion status. (p= 0.535) More extrathoracic metastasis was noted in fusion-positive patients than fusion-negative patients at the first time of recurrence. (46.2% vs. 35.8%, p= 0.539) The median progression free survival on EGFR tyrosine kinase inhibitor treatment after recurrence was 0.9 months in fusion-positive patients, which was significantly shorter than 10.2 months in EGFR mutation positive and 6.4 months in wild type patients..

      Conclusion
      This study shows significantly poorer DFS of ALK or ROS fusion positive patients in Asian never smoker lung adenocarcinoma patients. Development of ALK or ROS targeted adjuvant therapies in this subset of patients is needed to improve their poor survival after curative surgery.