Durable Response to Crizotinib in a Patient with Pulmonary Adenocarcinoma Harboring MET Intron 14 Mutation: A Case Report

Background: For patients with non-epidermal non-small-cell lung cancer (NSCLC), molecular alterations should always be investigated, especially in non-smokers, who have a very high frequency of targetable alterations (EGFR 52%; ALK 8% in particular). MET exon 14 alterations are identified in 3-4% of NSCLCs and MET gene amplification and high protein expression are associated with a poor prognosis. The French recommendations only authorize the use of capmatinib and crizotinib if the mutation concerns exon 14. However, several different types of mutation in exon 14 of MET and its flanking introns can induce a jump in exon 14, activate the MET gene and thus be sensitive to anti-MET tyrosine kinase inhibitors. Case Summary: This case concerns a 76-year-old Caucasian male with a medical history including idiopathic thrombocytopenic purpura, chronic myelomonocytic leukemia (CMML), atrial fibrillation, arterial hypertension, obesity (BMI 36kg/m2), and a 5-10 pack-per-year smoking history. A left upper lobe pulmonary nodule of 12.4 mm was discovered in March 2019. The patient received adjuvant chemotherapy with carboplatin AUC 5 and vinorelbine 25.00 mg/m2. At the end of the adjuvant treatment, the patient was in complete remission for 5 months. In February 2020, the CT scan revealed a mediastinal lymph node progression. A complementary molecular analysis was realized on the initial surgical specimen. A c.3082 +3A>T mutation in the MET gene was identified. This mutation confers susceptibility to antiMET tyrosine kinase inhibitors. Treatment with crizotinib was initiated with an initial dose of 250 mg/day for 15 days and then increased to 250 mg twice a day. After 7 months of treatment with crizotinib, the disease was still stable according to RECIST 1.1. Conclusion: We report here the original case of a patient presenting a lung adenocarcinoma with an intron 14 mutation and having a durable TKI response.