EML4-ALK fusion gene in lung adenocarcinoma: A retrospective analysis of the outcome of cisplatin plus pemetrexed treated patients.

Background: A subset of lung adenocarcinomas harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene EML4-ALK (ALK) which encodes an activated tyrosine kinase. To help identification of this gene within the NSCLC population of South Italy, we retrospectively examined its incidence in a cohort of lung adenocarcinomas, the clinical characteristics and treatment outcomes of pts who had a rearranged ALK. Methods: Ninety-six lung adenocarcinoma pts. (58 male, 38 female, median age 64 years), who received cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2) or cisplatin plus gemcitabine (1,250 mg/m2) every 21 days, were retrospectively analyzed. Cytology or histology samples were reviewed to reconfirm the diagnosis; ALK and EGFR amplification were identified by FISH. The ALK FISH positive samples were tested for EGFR and K-Ras mutations by DNA sequencing; ALK rearrangements were confirmed by immunohistochemistry for ALK expression. Results: Of 96 screened tumors 8 (8.3%) were EML4-ALK mutants; none of them showed EGFR and/or k-Ras mutations and all were detected in non smoking and younger men (median age 52 years, range 32-56). Within the EML4-ALK cohort all pts were treated with cisplatin plus pemetrexed. Two of evaluable pts. had a PR, four had SD and two had PD. At the time of this review the median TTP was 9 months and the median OS 17 months in ALK positive pts. The 32 ALK negative Cisplatin Pemetrexed treated pts achieved a median TTP of 6.2 months and a median OS of 11 months. Conclusions: According to our results ALK positive tumors may constitute a distinct entity among lung adenocarcinomas and be characterized by younger onset, absence of mutations in EGFR and RAS and prevalence in non or light smokers. Overall the presence of EML4-ALK fusion gene in our pts is suggestive of a better therapeutic outcome.