Expression of MET, IGF-1R, IL-6/gp130, and AXL in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations.

Abstract

7555 Background: We have observed a 70% response rate (RR) in NSCLC p with EGFR mutations treated with erlotinib. Primary resistance to erlotinib could result from the absence of an EGFR-organized network. Crosstalk and transactivation between other receptor tyrosine kinases, such as EGFR, IGF-1R and MET, is recognized as a mechanism of growth in several tumors. Mutant EGFR could activate the IL-6/gp130 pathway. Overexpression of AXL has been observed in NSCLC and in GIST imatinib-resistant tumors. Methods: The expression of MET, IGF-1R, IL-6/gp130 and AXL was examined by QPCR in the original pretreatment tumor biopsies of 98 NSCLC p with EGFR mutations. Expression levels by terciles were correlated with outcome to erlotinib. Results: There was a good correlation between the expression of IL-6/gp130 and AXL (r = 0.33; p = 0.001). No differences were observed in expression of the four genes according to gender, smoking history, type of EGFR mutation, or other clinical characteristics. The highest tercile of AXL expression was associated with a higher incidence of lung metastases (87.5%; p = 0.02). No other association between any of the genes and metastatic sites (including brain and bone) was observed. Overall RR was 70%, progression-free survival (PFS) was 14 months (m), and median survival (MS) was 27 m. No differences in RR, PFS or MS were observed according to the expression of any of the four genes. Conclusions: The coactivation of other receptor tyrosine kinases seems not to affect the initial outcome to erlotinib in NSCLC p with EGFR mutations. The association of high levels of AXL with lung metastases should be further examined, since AXL expression has been correlated with metastasis to the lung in a breast cancer model. The addition of AXL inhibition could be a novel treatment approach for enhancing the effect of erlotinib in p with EGFR mutations. No significant financial relationships to disclose.