Detection of Crizotinib-Sensitive Lung Adenocarcinomas With MET, ALK, and ROS1 Genomic Alterations via Comprehensive Genomic Profiling.

Introduction: Crizotinib is an oral multitargeted tyrosine kinase inhibitor (TKI) with activity against lung cancers driven by -rearrangements, -rearrangements and -amplification. Comprehensive genomic profiling (CGP) based on clinical next generation sequencing (NGS) can detect crizotinib-sensitive genomic changes. We describe use of CGP to identify tumors responsive to crizotinib.

Methods: Retrospective review of representative lung adenocarcinomas treated with crizotinib and assayed with a clinical NGS assay.

Results: We report 3 cases of lung adenocarcinoma; one each identified to harbor an -rearrangement (), -rearrangement () and -amplification by genomic profiling. Notably, the -amplification was only detected by CGP as subsequent FISH testing did not show amplification. CGP also revealed other common genomic changes (somatic mutations [ in 2 cases], deletions [ in 1 case], amplifications [ in 1 case] and variants of unknown significance) in these cases. All patients received crizotinib 250 mg twice daily and achieved radiographic tumor reduction for months. The case harboring amplification of 10 copies achieved partial response and is one of the first -amplified lung cancer responsive to crizotinib in which the sole detection method was CGP.

Conclusions: CGP holds the promise of detecting predictive genomic alterations (somatic mutations, copy number changes and rearrangements) that may underlie tumor dependency in an oncogene and govern response to clinically-available TKIs for lung adenocarcinomas.