Case Report: Durable partial response to icotinib plus crizotinib in a lung adenocarcinoma patient with double uncommon EGFR G719D/L861Q mutations and an acquired novel CUX1-MET fusion

Non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping or high MET amplification display a high rate of response to MET inhibitors. However, MET fusions in NSCLC have rarely been revealed. In this report, a 63-year-old woman with lung adenocarcinoma (LADC), harboring EGFR exon 18 G719D and exon 21 L861Q mutations, received first-generation, EGFR-tyrosine kinase inhibitor (TKI) icotinib therapy. Next generation sequencing (NGS) results only displayed an EGFR T790M point mutation following icotinib resistance. Thus, the patient was treated with osimertinib and achieved a stable disease (SD). However, disease progressed after 15 months and a novel MET fusion (CUX1 exon14-MET exon15) in addition to EGFR G719D/L861Q mutations were simultaneously detected in a tissue biopsy sample. After more than nine months, the patient subsequently achieved a PR with the combination of icotinib and crizotinib. To our knowledge, this is the first case of LADC patient displaying the presence of EGFR double uncommon mutations and an acquired novel CUX1-MET fusion that has benefited from icotinib plus crizotinib treatment. Following nine months of PR with icotinib plus crizotinib, the patient, until the time of publication, is exhibiting stable disease. The results suggest that the CUX1-MET fusion may be sensitive to crizotinib, although previous reports indicated that some MET fusion cases did not respond to crizotinib. Given this disparity, distinguishing MET fusion partners when crizotinib is used in LADC treatment is also very important.