ALK amplification and crizotinib sensitivity in non-small cell lung cancer cell lines and patients report.

Abstract

10556 Background: ALK high copy number (HCN) seems to be a frequent event, described in 13-17% of Non-small cell lung cancer (NSCLC). The goal of this study was to describe ALK genomic aberrations on NSCLC patients and cell lines, to explore the ALK HCN response to crizotinib through in vitro assays and to report three patients case. Methods: 191 Paraffin embedded specimens from advanced NSCLC patients and 27 NSCLC cancer cell lines were screened for ALK copy number by fluorescent in situ hybridization (FISH). Crizotinib sensitivity was evaluated in 9 cell lines through WST1 assays and clonogenic tests. Three patients exhibiting ALK HCN were assessed for response to crizotinib. Results: EML4-ALK translocation was present in 22 pts (11.5%). 21 pts (11%) exhibited over 6 copies of ALK. 6 (22%) cell lines displayed more than 5 copies of ALK, 19 (70%) presented a gain of 3 or 4 ALK copy number, only one cell line exhibited normal ALK copies and one harbored EML4-ALK translocation. FISH with CEP2 revealed a polysomy of chromosome 2 in cases with ALK HCN.Out of the 9 cell lines tested, 4 ALK HCN cell lines (H661, A427, BEN, H1299) exhibited increased sensitivity for crizotinib vs. 3 low ALK copy number (LCN) cell lines (H1975, H1651, H1650) with a low sensitivity. Median IC50 with crizotinib values was1750 nM [300-2800nM] in ALK HCN cell lines vs 4500 nM [800-8000nM] in ALK LCN cell lines, p=0.35. 3 patients with ALK HCN tumor received crizotinib ( in 4th , 5th and 6th -line therapy) for 2, 3 and 5 months with stable disease as best response and clinical benefit in 2 pts. Conclusions: ALK HCN may predict sensitivity to crizotinib. A clinical study is planned in ALK HCN pts.