Therapeutic Challenges in Metastatic Non-small Cell Lung Cancer (NSCLC) With Concurrent Mesenchymal-Epithelial Transition Factor (MET) Amplification and High Programmed Death-Ligand 1 (PD-L1) Expression: A Case Study.

Mesenchymal-epithelial transition factor (MET) amplification is an uncommon but important oncogenic driver in non-small cell lung cancer (NSCLC), and its coexistence with high programmed death-ligand 1 (PD-L1) expression creates a therapeutic dilemma over how to sequence MET-directed therapy and immune checkpoint inhibition. We report a 65-year-old man who presented with weight loss, hoarseness with left vocal cord palsy, and right supraclavicular lymphadenopathy, with metastatic disease in the lungs, lymph nodes, and bone (with hepatic and brain metastasis emerging later on therapy). Biopsy confirmed metastatic lung adenocarcinoma. Comprehensive genomic profiling (CGP) showed MET amplification (copy number gain of 8, an intermediate-level amplification), a TP53 mutation, and high PD-L1 expression (tumor proportion score (TPS) ~80% by 22C3 immunohistochemistry at diagnosis and a VENTANA SP142 tumor cell (TC) score of 90% at progression; the two assays are not directly comparable). Because the CGP and PD-L1 results returned only after treatment had started, first-line platinum-doublet chemotherapy (nab-paclitaxel/carboplatin) was given, with a mixed response and a new hepatic metastasis. Second-line atezolizumab plus pemetrexed/carboplatin produced a partial response, followed by brain metastases. Third-line off-label capmatinib, used despite the absence of a MET exon 14 skipping mutation, produced a marked systemic response following brain radiotherapy and subsequent capmatinib. The patient then developed hepatic dysfunction that, against a background of concurrent radiological liver progression, was of uncertain cause; capmatinib was reduced and stopped, and he died approximately 30 months after diagnosis from liver failure and sepsis. This case illustrates the difficulty of sequencing therapy when MET amplification and high PD-L1 expression coexist. Notably, a marked response to capmatinib occurred despite an intermediate MET copy number below the threshold usually associated with benefit. Any role for combined or sequential MET inhibition and immunotherapy remains a hypothesis requiring prospective study rather than a conclusion supported by this single case, and cross-assay PD-L1 results should be interpreted with caution.