Comparative analyses of overall survival of anaplastic lymphoma kinase (ALK)–positive advanced non-small cell lung cancer (NSCLC) patients who did not receive ALK inhibitors.

Abstract

7515 Background: There have been limited data on the overall survival (OS) of ALK gene rearranged (ALK-positive) NSCLC patients who did not receive ALK inhibitors. We investigated the OS of advanced ALK-positive NSCLC patients who were managed in the pre-ALK inhibitors era. Methods: This is a retrospective case-case study of ALK-positive patients vs. ALK wildtype (WT) comparators who were treated in Seoul National University Hospital (SNUH), Seoul, Korea. A total of 1,100 stage IIIB/IV patients with non-squamous histology were collected in the NSCLC database of SNUH between 2003 and 2009. To enrich for ALK-positive cases, we performed ALK FISH on 257 cases that were either EGFR WT or non-responders to prior EGFR tyrosine kinase inhibitor (TKI) therapy. We compared survival outcomes between 3 groups of patients: 1) ALK-positive, 2) EGFR mutation positive (EGFR mut+), and 3) ALK WT/EGFR WT. For each comparison, 1 ALK-positive patient was matched to 2 EGFR mut + and 2 ALK WT/EGFR WT patients based on: age at diagnosis, sex, and stage. Progression-free survival (PFS) of 1st-line chemotherapy and EGFR TKIs were also analyzed. Results: Twenty two cases were ALK-positive by FISH and did not receive ALK inhibitors during the follow-up period. The median OS of ALK-positive (n=22), EGFR mut+ (n=44), and ALK WT/EGFR WT (n=44) patients was 10.4, 28.0, and 14.5 months, respectively (P-value; vs. EGFR mut+: 0.012, vs. ALK WT/EGFR WT: 0.384). The PFS of 1st-line platinum-based chemotherapy for the 3 groups was not different. However, the PFS of EGFR TKIs was shorter in ALK-positive patients, compared with the 2 other groups (P-value; vs. EGFR mut+: < 0.001, vs. ALK WT/EGFR WT: 0.048) Conclusions: In the pre-ALK inhibitor era, ALK-positive patients experienced the shortest survival. Although their responses to platinum-based chemotherapy were not different from comparator groups, they were even more resistant to EGFR TKI treatment than were ALK WT/EGFR WT patients.