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

Background: inhibitors such as vebreltinib. Case Description: amplification was not present at baseline but appeared after lorlatinib treatment, confirming it as an acquired rather than intrinsic resistance mechanism. Due to complications, such as elevated transaminase (an indication of hepatotoxicity), hyperlipidemia, and depression, that occurred during the patient's first-line treatment, combined ALK- and MET-TKI targeted therapy was not administered. Subsequent second-line treatment with single-agent vebreltinib failed to halt disease progression. After thorough systemic evaluation, a combination regimen of lorlatinib and vebreltinib was initiated, resulting in sustained partial remission (PR), excellent treatment tolerance, and notable improvement in quality of life. Conclusions: amplification, enabling sustained clinical remission. This case highlights the importance of repeat biopsy to identify acquired resistance mechanisms arising from intratumoral heterogeneity in response to targeted therapy, which is critical for making clinical decisions and adjusting treatment plans for patients with NSCLC.