Is there a place for crizotinib in c-MET alterations? A case of efficacy in ALK positive NSCLC patient with secondary c-MET amplification

Recently, Moro-Sibilot et al.1 presented the results of the AcSé study that evaluated the efficacy of crizotinib in non-small-cell lung cancer (NSCLC) with ROS1 fusions and c-MET mutations or overexpressions. The excellent performance of crizotinib in ROS1 fusions was confirmed. Nevertheless, in the c-MET cohort there was a lack of activity which was not sufficient to justify its use as targeted therapy in this population. Similar results were found in the analogous METROS trial.2
Despite this evidence, we present a case where crizotinib showed clinical activity, even in a life-threatening condition, thanks to double anaplastic lymphoma kinase (ALK) and c-MET inhibition. READ ARTICLE

Annals of Oncology DOI:10.1016/j.annonc.2019.11.016

Authors: M.Mazzotta, M.Filetti, A.Rossi, M.Roberto, M.Occhipinti, A.Pernazza, A.Di Napoli, S.Scarpino, A.Vecchione, R.Giusti, P.Marchetti

EditorialKirk SmithMarch 1, 2020Crizotinib, c-MET alteration, ALK positive NSCLC, secondary c-MET amplification

EP108-07 Correlation Between Genetic Profiling and Response in Danish ALK-Positive NSCLC Patients Treated with Crizotinib

In 2011 Crizotinib received FDA approval for the treatment of ALK-positive NSCLC. Due to large diversity in clinical course of these patients, baseline genomic profiling at diagnostic biopsy was performed to find possible correlations with clinical features. We performed a retrospective analysis of 28 consecutive patients receiving Crizotinib for metastatic, immunohistochemistry (IHC)- and fluorescens in-situ hybridization (FISH)-determined ALK-positive NSCLC, between September 2011 and DATE. Clinical data were collected by chart review. DNA/RNA genomic profile were performed using the patients’ biopsy at the time of diagnosis or at initiation of therapy using targeted next-generation sequencing (NGS) Oncomine™ Focus (ThermoFisher Scientific) and Archer® Solid Tumor (ArcherDx) assays. Baseline clinical features and genetic information were correlated with overall survival and progression free survival. Although this small cohort does not allow to draw unambiguous conclusions, it does i..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2196

Authors: L. Melchior, E. Santoni Rugiu, J. Sørensen, J. Bjerregaard, E. Urbanska

Kirk SmithOctober 1, 2019ALK positive NSCLC, DNA-NGS, RNA-NGS