| Background and objectives:Mesenchymal-epithelial transition factor(MET)gene amplification or the MET exon 14 skipping mutation are considered to be the other important molecular therapeutic target for non-small cell lung cancer(NSCLC),following anaplastic lymphoma kinase(ALK)and epidermal growth factor receptor(EGFR)gene mutation.Previous studies have shown that Crizotinib is effective and well tolerated in patients with advanced NSCLC with MET gene amplification or MET exon 14 skipping mutation.The purpose of this study was to analyze the clinicopathological characteristics,efficacy and safety of Crizotinib in the treatment of advanced and metastatic non-small cell lung cancer(NSCLC)patients with MET gene amplification or MET exon 14 skipping mutation in Liaoning,and provide theoretical support for clinical decision-making.Methods: From June 1,2017 to November 30,2019,20 patients with advanced NSCLC who received MET gene amplification or MET exon 14 skipping mutation were collected from some top three hospitals in Liaoning region.All patients were pathologically or radiographically diagnosed as NSCLC receiving crizotinib until the condition progressed or intolerable adverse reaction.the efficacy was evaluated every 2 cycles(56 d).The clinicopathological features included: age,sex,smoking history,pathological type,ECOG score.Safety indicators include the classification,grading of adverse reactions and the reduction or withdrawal of drugs due to adverse reactions.The short-term outcome measures were objective remission rate(objective response rate,ORR),disease control rate(disease control rate,DCR),and long-term outcome measures were progression-free survival(progression free survival,PFS)and overall survival(overall survival,OS).The efficacy was evaluated according to the solid tumor evaluation standard RECIST1.1,and the adverse drug reaction grade was based on the CTCAE.The follow-up method includes access to inpatient,outpatient records and telephone,with a deadline of 30 November 2019.SPSS22.0 software was used for statistical analysis,and descriptive analysis was used in this study.survival of the patients using Graphpad Prism 5.0 to draw survival curves as well as survival analysis.Results:1.Clinicopathological features:There were 12 patients in the MET gene amplification group,The median age was 64.5 years;10 male patients(83.3%)and2 female patients(16.7%);9 smokers(75.0%)and 3 non-smokers(25.0%);10adenocarcinoma patients(83.4%),1 adenosquamous carcinoma(8.3%)and 1squamous carcinoma(8.3%);9 patients(75.0%)with ECOG score of 0-2,3patients(25.0%)with ECOG score of 3-4;2 patients with non-operable stage III(16.7%),10 patients with stage IV(83.3%);9 patients with first-line treatment(75.0%),3 patients with second-line and above treatment(25.0%);there were 3patients with EGFR sensitivity mutation(25.0%),9 patients without EGFR sensitivity mutation(75.0%);5 patients with low-level amplification(41.7%),7patients with medium level amplification(58.3%).There were 8 cases in MET exon 14 skipping mutation group,The median age was 73 years old;3 cases were male(37.5%),5 cases were female(62.5%);3 cases were smokers(37.5%),5cases were non-smokers(62.5%);3 cases were adenocarcinoma(37.5%),1 case was adenosquamous carcinoma,1 case was sarcoma and 1 case was neuroendocrine carcinoma(12.5%),2 cases were unknown in pathological type(25%);7 patients(87.5%)with ECOG score of 0-2,and 1 patient(12.5%)with ECOG score of 3 or higher;1 patient(12.5%)with inoperable stage III and 7patients(87.5%)with stage IV;7 patients(87.5%)with Crizotinib as first-line treatment and 1 patient(12.5%)with line 2 or above;all patients did not have EGFR sensitive mutation.2.Efficacy: In the MET gene amplification group,the response rate(ORR)was 54.5%,the disease control rate(DCR)was 90.9%;In the MET exon 14 skipping mutation group,the response rate(ORR)was 50.0%,the disease control rate(DCR)was 87.5%.MET gene amplification patients were better than MET exon 14 skipping mutation group patients in ORR and DCR,but it was not statistically significant(P values were 0.845 and 0.811,respectively).In the MET gene amplification group,the median time to progression free of disease(m PFS)was 9.0 months.The median OS was 9.3 months.In the MET exon 14 skipping mutation group,the median time to progression free of disease(m PFS)was 10.0months,The median OS was 12.9 months.MET exon 14 skipping mutation patients were better than MET gene amplification patients in PFS and OS,but it was not statistically significant(P=0.503 and 0.627,respectively).3.Adverse reactions: The overall safety was good.In the MET gene amplification group,the common adverse reactions included nausea and vomiting(25%),diarrhea(8.3%),increase of glutamic oxaloacetate and alanine aminotransferase(16.7%),fatigue(16.7%),bradycardia(8.3%),taste abnormality(8.3%),interstitial pneumonia(16.7%),constipation(8.3%),wasting(8.3%).Most of the adverse reactions were grade 1-2,and there were less of grade 3 and above,including interstitial pneumonia(8.3%)and transaminase elevation(8.3%).Most of the patients were tolerable to the adverse reactions;1 patient was decreased due to the rise of level 3 transaminase;1 patient was decreased due to continuous bradycardia;1 patient was stopped due to severe interstitial pneumonia;1 patient was stopped due to emaciation.In the MET exon 14 skipping mutation,the adverse reactions included: nausea and vomiting(12.5%),diarrhea(12.5%),increased glutamic oxaloacetate transaminase,increased glutamic pyruvate transaminase(37.5%),fatigue(25.0%),bradycardia(25.0%),limb edema(25.0%),skin rash(25.0%),visual abnormality(12.5%),anemia(12.5%),hypoproteinemia(12.5%),prolonged QTc interval(25.0%).In one case,the drug was suspended due to grade4 liver function abnormality,and the dosage was reduced after the symptomatic treatment of liver function recovered to grade 3;in one case,the dosage was reduced due to bradycardia;in one case,the dosage was reduced due to QTc interval extension.Conclusion:1.The patients with MET gene amplification are mostly seen in men,smokers and patients with lung adenocarcinoma,and there was co-mutation with EGFR sensitive gene;the patients with MET exon 14 skipping mutation were older,women and patients with adenocarcinoma more common,and no co-mutation of EGFR sensitive gene was found.2.The efficacy of Crizotinib was better in patients with MET gene amplification and MET exon 14 skipping mutation.The ORR and DCR of patients with MET gene amplification patients were better than MET exon 14 skipping mutation patients.The PFS and OS of patients with MET exon 14 skipping mutation patients were better than MET gene amplification patients.In the MET amplification group,the ORR of the patients with middle-level MET amplification was better than the patients with low-level amplification.3.The patients who received Crizotinib had better tolerance and controlled adverse reactions. |
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