A Retrospective Study Of Endostar Combined With Chemotherapy In The First-Line Treatment Of EGFR,ALK,ROS-1 Mutation-Negative Stage Ⅳ NSCLC And Exploration Of Its Clinical Benefit Predictors

Objective:Lung cancer is the malignant tumor with the highest incidence and mortality in the world,and non-small cell lung cancer accounts for about 80%-90%.In recent years,targeted therapy,anti-angiogenesis and immunotherapy provide more treatment options for patients with advanced NSCLC,but for patients with negative genes,chemotherapy combined with anti-angiogenesis is still one of the preferred treatment option.Endostar has been used in clinic for more than ten years,and several prospective studies have confirmed that Endostar combined with platinum-containing dual-drug chemotherapy is more effective than chemotherapy alone in the treatment of stage Ⅳ NSCLC.However,these studies were carried out earlier,no driver gene restriction was made.We retrospectively analyzed one hundred fifty stage Ⅳ NSCLC patients with negative EGFR,ALK and ROS-1mutations in our center,and evaluated the efficacy and safety of Endostar combined with chemotherapy in these patients.This study also analyzed the peripheral blood cell count ratio of patients before receiving treatment,aiming to explore the predictors of clinical benefit of Endostar combined with chemotherapy.Method:The clinical data of one hundred fifty patients with EGFR,ALK and ROS-1mutation-negative stage Ⅳ NSCLC who were admitted to the affiliated Hospital of Qingdao University from January 2016 to December 2018 were retrospectively collected.Among them,fifty nine patients in the combination group were received Endostar combined with platinum-containing dual-agent chemotherapy,and ninety one patients in the control group only received platinum-containing dual-agent chemotherapy.We used response evaluation criteria in solid tumors(RECIST1.1)to evaluate the curative effect of tumor treatment.The survival status and survival time of patients were followed up through telephone follow-up and electronic medical record system.The primary research endpoints are progression free survival,objective response rate and disease control rate;the secondary research endpoints are overall survival,safety and toxicity.We used Kaplan-Meier method to draw the survival curves,and the Log-rank method to test the survival differences.COX regression model was used for univariate analysis and multivariate analysis.Collect the peripheral blood cell count data of the patient before the first cycle treatment,and obtain the neutrophil to lymphocyte ratio(NLR),neutrophil to white blood cell ratio(NWR),platelet to lymphocyte ratio(PLR),platelet to white blood cell ratio(PWR),monocyte to lymphocyte ratio(MLR),monocyte to white blood cell ratio(MWR),and lymphocyte to white blood cell ratio(LWR).Receiver operating curves(ROCs)were used to determine the optimal cut-off values of the above seven indicators.According to the cut-off value,the survival differences were analyzed in groups.Result:1.Compared with the control group,the mPFS of patients in the combination group was extended by 1.60 months(7.30 months vs 5.70 months,P=0.034).Among them,the mPFS of adenocarcinoma patients in the combined group was 2.60 months longer than that in the control group(8.00 months vs 5.40 months,P < 0.001),and there was no significant difference in mPFS of squamous cell carcinoma patients between the two groups.2.The total DCR of the combined group was better than that of the control group(96.6% vs 84.6%,P=0.040)and there was no difference in ORR(32.2% vs 20.9%,P =0.119).Among them,the ORR of adenocarcinoma patients in the combined group was better than that of the control group(42.4% vs 21.3%,P=0.042),the DCR was better than that of the control group(100% vs 84.6,P = 0.038);there were no differences in ORR(19.2% vs 20.5%,P=0.902)and DCR(84.6% vs 91.1%,P=0.453)between the combined group and the control group of patients with squamous cell carcinoma.The DCR of the combined group was better than that of the control group(100% vs 84.4%,P= 0.037)and no difference in ORR(32.2% vs 20.9%,P=0.098)in patients who used pemetrexed / platinum;the ORR and DCR were no significant differences between the combined group and the control group in the patients who used gemcitabine / platinum or paclitaxel / platinum.3.According to the ROCs,the best cutt-off value of hematological indexes in the combined group was determined,and each indexes was divided into high and low group.The mPFS of high NWR group was extended by 2.30 months than that of low NWR group(8.70 months vs 6.40 months,P = 0.013),high NLR group was extended by 2.30 months than that of low NLR group(8.70 months vs 6.40 months,P = 0.004),low LWR group was extended by 2.00 months than that of high LWR group(8.00 months vs 6.00 months,P = 0.048).The m OS of low MLR group was extended by 5.50 months than that of high MLR group(16.70 months vs 11.20 months,P = 0.015).There were no differences in PFS and OS between PWR,PLR and MWR groups.4.The incidence of hematological toxicity in the combination group and the control group was similar,and the difference was not statistically significant.Conclusion:1.Endostar combined with platinum-containing dual-agent chemotherapy regimen in EGFR,ALK,ROS-1 mutation-negative stage Ⅳ lung adenocarcinoma can improve the objective response rate and disease control rate,prolong the median progression free survival time,reduce the risk of disease progression,and do not increase hematological toxicity.2.In the combination group,the patients with higher NWR,higher NLR and lower LWR had longer mPFS,and who with lower MLR had longer m OS.Therefore,NWR,NLR,LWR and MLR before treatment can be used as prognostic predictors of the efficacy of Endostar combined chemotherapy in EGFR,ALK and ROS-1mutation-negative stage Ⅳ NSCLC.