Study On The Efficacy And Safety Of Targeted Therapy For Advanced Non-Small Cell Lung Cancer With MET Gene Mutation

Objective The aim of our study was to assess the efficacy and safety of MET TKI targeted therapy for advanced non-small cell lung cancer with different types of MET gene mutation.Methods We retrospectively analyzed the data of the patients with advanced non-small cell lung cancer(NSCLC)with MET gene mutation.They were divided into MET exon 14 skipping mutation(31 cases)and MET gene amplification or protein overexpression(37 cases).Follow-up to disease progression or death,SPSS26.0 software was used for statistical analysis,Chi-square test was used to compare clinical characteristics,efficacy and adverse reactions,Kaplan-Meier method was used to analyze progression-free survival and total survival,and Cox regression model was used to analyze progression-free survival of MET exon 14 skipping mutation.Results The ORR of MET exon 14 skipping mutation group and MET amplification or protein overexpression group were 58.1%and 32.4%,with significant difference(p<0.05).DCR were 93.5%and 86.5%,with no significant difference(p>0.05).The DCR of type Ib targeted drugs(Sevotinib,Gumetinib,Beretinib,Tepotinib)were better than that of type Ⅰa targeted drug(Clozolitinib),with no statistically significant difference(p>0.05).(2)The median PFS of patients with MET exon 14 skipping mutation was longer than that of patients with MET gene amplification or protein overexpression(PFS:10.3 months vs 6.5 months,p=0.329,p>0.05).There was no statistically significant difference in the median OS between patients with MET exon 14 skipping mutation and those with MET gene amplification or protein overexpression(OS:34.4 months vs not yet reached,p=0.854,p>0.05).OS needs to wait for follow-up.(3)The common side effects of the two groups of patients include(more than 20%):fatigue,nausea and vomiting,diarrhea,anorexia,edema,elevated transaminase,and rash.There was no statistically significant difference between the two groups(p>0.05).(4)Univariate analysis showed that the PFS of patients with different ECOG scores,pathological types,smoking or not,and the number of treatment lines in the MET exon 14 skipping mutation group who received MET TKI targeted treatment had statistically significant differences(all p<0.05).There was no statistically significant difference in PFS between the patients receiving MET TKI targeted treatment with MET amplification or protein overexpression and those with different age,sex,ECOG score,pathological type,metastasis,smoking or not,and the number of treatment lines(p>0.05).Multivariate analysis showed that the patient’s ECOG score and the number of treatment lines were independent prognostic factors of MET TKI treatment for advanced lung cancer with MET exon 14 skipping mutation,and the difference was statistically significant(p<0.05).Conclusion MET TKI targeted therapy were effective for advanced lung cancer patients with MET exon 14 skipping mutation and advanced lung cancer patients with MET amplification or protein overexpression,and the former is more effective.The toxicity and side effects of the two groups were well tolerated.For advanced non-small cell lung cancer with MET gene mutation,MET TKI targeted therapy will be a very promising therapeutic drug.