Improved Survival Outcomes in Patients With MET-Dysregulated Advanced NSCLC Treated With MET Inhibitors: Results of a Multinational Retrospective Chart Review

In this retrospective study, MET inhibitor therapy demonstrated better survival outcomes compared with other treatments like chemotherapy and immunotherapy. Furthermore, MET ex14 skipping mutations and/or MET amplification typically occurred in the absence of other oncogenic driver mutations. With recent approvals of METi for patients with MET ex14 NSCLC, there is a need to identify more patients for treatment with METi to improve survival outcomes. Background: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET -dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting. Patients and Methods: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET -dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms. Results: Overall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations ( MET ex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for MET ex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the MET ex14 cohort; 13% in the MET -amplified only cohort). In the MET ex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET -amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479). Conclusions: MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET -dysregulated NSCLC.

Automated summary

MET inhibitor therapy has shown better survival outcomes in patients with MET -dysregulated NSCLC. MET ex14 skipping mutations and/or MET amplification usually occur without other oncogenic driver mutations.