ALK-tyrosine kinase inhibitor intrinsic resistance due to de novo MET-amplification in metastatic ALK-rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination—case report

Background: ) gene, which is a still elusive and underrecognized mechanism of primary resistance to ALK-TKIs. Case Description: v.1, combined second-line treatment with alectinib and the MET-TKI, crizotinib, was implemented resulting in very pronounced objective response, significantly improved quality of life, and no adverse events so far during the ongoing treatment (6 months). Conclusions: amplification. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment.