ALK-tyrosine kinase inhibitor resistance due to acquired MET amplification in ALK-fusion positive advanced NSCLC effectively treated by lorlatinib-vebreltinib combination: a case report and literature review

Molecular testing has become an essential part of managing non-small cell lung cancer (NSCLC). The detection of EGFR, BRAF, and MNNG HOS transforming gene (MET) mutations, and the analysis of anaplastic lymphoma kinase (ALK), ROS1, RET, and NTRK rearrangements have been incorporated into NSCLC diagnostic standards, and inhibitors of these kinases are used routinely in clinical practice. Although targeted therapies, represented by ALK-tyrosine kinase inhibitor (ALK-TKI), have significantly improved the prognosis of ALK-positive NSCLC patients, acquired resistance (such as MET amplification) remains a core challenge faced by clinicians. Currently, there is no standardized treatment regimen established in Chinese and international clinical guidelines for patients with ALK-TKI resistance caused by MET amplification. Although clinical practice has attempted to combine targeted drugs for MET amplification, such as crizotinib, with first and second-generation ALK-TKIs and observed preliminary efficacy, there is no published research on the combination of third-generation ALK-TKI lorlatinib with new MET inhibitors such as vebreltinib.