| BackgroundLung cancer is the most common malignancy in the world and remains the leading cause of malignant tumor death.Non-small cell lung cancer(NSCLC)is the most common pathological type,and most patients are advanced at the time of presentation.People with type 2 diabetes mellitus are at higher risk of developing certain malignant tumors than those with normal blood glucose,and patients with malignant tumors plus type 2 diabetes have a worse prognosis.Studies have shown that different hypoglycemic drugs have different effects on cancer risk and prognosis.The use of metformin can reduce the risk of cancer morbidity and mortality.In this study,we will retrospectively study the effect of metformin on first-line chemotherapy and EGFR-TKI therapy in patients with advanced NSCLC plus T2DM.MethodsIn the first part,this study retrospectively analyze the clinical data of 137 patients with stage ?B/? NSCLC plus T2DM who received first-line chemotherapy with platinum drugs from Qilu Hospital of Shandong University from 2005 to 2018.Patients were divided into two groups:group A(n = 92)received metformin;group B(n = 33)received other hypoglycemic agents,Then,we evaluate the differences of objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),and overall survival(OS)between the two groups.In the second part,we retrospectively analyze the clinical data of patients with stage ?B/? lung adenocarcinoma with T2DM who received first-line EGFR-TKI treatment from Qilu Hospital of Shandong University from 2013 to 2018.Patients were divided into two groups:group a(n = 43)received metformin;group b(n = 28)received other hypoglycemic agents,Then,we evaluate the differences of ORR,DSR,PFS and OS between the two groups.Data statistics and analysis were performed using SPSS 25.0 software.ResultsIn the first part,in the patients with stage IIIB/IV NSCLC combined with T2DM receiving first-line chemotherapy with platinum drugs,the metformin group(group A)had a ORR of 44.6%(41 persons)and a DCR of 83.7%(77 persons).The ORR of group B was 24.4%(11 persons),DCR was 66.7%(30 persons).After chi-square test,we found that ORR(p = 0.02)and DCR(p = 0.02)were statistically different between the two groups.The chemotherapy effect of group A was significantly better than that of group B.The overall median PFS of the metformin group(group A)and the non-metformin group(group B)was 9.8 months(95%CI[8.4-11.1]months).The median PFS for group A was 10.6 months(95%CI[8.9-12.3]months).The median PFS for group B was 6.1 months(95%CI[4.9-7.2]months).The 1-year PFS rate of group A was 42.1%.The 1-year PFS rate of group B was 27.0%.The PFS of group A was significantly longer than that of group B(p = 0.03).After Cox univariate regression analysis of general characteristics,clinical and treatment characteristics,the effect of basic fasting blood glucose(>7.0 mmol/1)on PFS was found(HR=1.579,95%CI[1.023-2.436];p = 0.04).Considering that factor,Cox multivariate regression analysis found that using metformin(HR=0.585,95%CI[0.378-0.906];p = 0.02)was an independent protective factor affecting PFS,and poor fasting glycemic control(>7.0 mmol/1)(HR=1.668,95%CI[1.075-2.586];p = 0.02)was an independent risk factor for PFS.The overall median OS of the metformin group(group A)and the non-metfomin group(group B)was 17.9 months(95%CI[13.9-22.0]months).The median OS of group A was 18.4 months(95%CI[12.5-24.3]months).The median OS of group B was 14.0 months(95%CI[6.1-21.9]months).The 1-year OS rate of group A was 71.7%.The 1-year OS rate of group B was 56.4%.The OS of group A was longer than group B(p =0.048).After Cox univariate regression analysis of general characteristics,clinical and treatment characteristics,the effect of basic fasting blood glucose(>7.0 mmol/1)on OS was found(HR=1.647,95%CI[1.048-2.589];p = 0.03).The effect of smoking history on OS was found(HR=1.685,95%CI[1.120-2.537];p =0.01).The effect of clinical stage on OS was found(HRF=1.618,95%CI[1.071-2.445];p = 0.02).Considering that factors,Cox multivariate regression analysis found that poor fasting glycemic control(>7.0 mmol/1)(HR=1.745,95%CI[1.104-2.757];p = 0.02),smoking history(HR=1.996,95%CI[1.307-3.049];p = 0.001),clinical stage(HR=1.738?95%CI[1.143-2.642];p = 0.01)are independent risk factors for OS.The use of metformin(HR = 0.632,95%CI[0.416-0.961];p = 0.03)was an independent protective factor affecting OS.In the second part,in patients with stage ?B/? lung adenocarcinoma with T2DM treated with first-line EGFR-TKI,the ORR of the metformin group(group a)was 44.2%(19 patients).The DCR was 81.4%(35 patients).The ORR of the non-metformin group(group b)was 17.9%(5 persons),and the DCR was 67.9%(19 patients).After the chi-square test,we found that ORR(p = 0.04)was statistically different between the two groups,DCR(p =0.19)was not statistically different,and group a had a better objective response rate.The overall median PFS of the metformin group(group a)and the non-metformin group(group b)was 10.1 months(95%CI[6.04-14.30]months).The median PFS for group a was 11.2 months(95%CI[6.1-16.3]months).The median PFS for group b was 6.4 months(95%CI[2.5-10.3]months).The 1-year PFS rate of group a was 46.5%.The 1-year PFS rate of group b was 35.7%.The PFS of group A was significantly longer than that of group B(p = 0.03).The overall median OS of the metformin group(group a)and the non-metformin group(group b)was 20.6 months(95%CI[16.7-24.6]months).The median OS of group a was 25.2 months(95%CI[11.4-39.0]months).The median OS of group b was 20.0 months(95%CI,[17.1-22.9]months).The 1-year OS rate of group a was 79.1%.The 1-year OS rate of group b was 75.0%.There was no significant difference between group a and group b(p = 0.15).Conclusion1.The use of metformin can increase the ORR and DCR of patients with stage IIIB/IV NSCLC plus T2DM receiving platinum-based dual-agent first-line chemotherapy,and prolong PFS and OS.2.Poor control of fasting blood glucose levels is an independent risk factor for PFS in patients with stage IUB/IV NSCLC plus T2DM who receive first-line chemotherapy with platinum3.Poor control of fasting blood glucose levels,smoking history,and clinical staging are independent risk factors for OS in patients with stage ?B/? NSCLC plus T2DM receiving platinum-based first-line chemotherapy.4.The use of metformin is an independent protective factor affecting PFS and OS in patients with stage ?B/?NSCLC combined with T2DM receiving first-line chemotherapy with platinum.5.The use of metformin can improve the ORR of patients with advanced lung adenocarcinoma plus T2DM treated with first-line EGFR-TKI and prolong PFS.6.The use of metformin does not improve DCR or prolong OS of patients with advanced lung adenocarcinoma plus T2DM treated with first-line EGFR-TKI. |
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