A Real-world Study Of First-line Bevacizumab Combined With Chemotherapy And Its Clinical Prognostic Prediction Factors In Patients With Advanced Non-squamous NSCLC

PurposeChemotherapy-based therapy is the main treatment mode of advanced non-small cell lung cancer(NSCLC),and the emergence of antiangiogenic therapy has improved the prognosis of patients with advanced NSCLC,especially for driver gene-negative advanced non-squamous NSCLC.Bevacizumab is a recombinant monoclonal antibody that inhibits tumor angiogenesis by blocking the signal pathway between vascular vascular endothelial growth factor(VEGF)and its receptor.At present,a number of clinical studies of high-dose(15mg/kg)bevacizumab combined with chemotherapy for advanced non-squamous NSCLC patients have been carried out,but the studies of low-dose(7.5mg/kg)bevacizumab are few and they were carried out earlier.Low-dose bevacizumab has insufficient data in real-world clinical practice,and the efficacy biomarkers of bevacizumab are unclear.Therefore,the purpose of this study is to supplement the real-world data of patients with driver gene-negative advanced non-squamous NSCLC treated with low-dose bevacizumab combined with chemotherapy,and explore the prognostic predictors to find the dominant population of bevacizumab and achieve more precise personalized treatment.MethodA retrospective study was perfermed on driver gene-negative stage IV non-squamous NSCLC patients diagnosed at the affiliated hospital of Qingdao University from January2016 to December 2019.They were divided into two groups according to the treatment protocol: chemotherapy group and bevacizumab combined with chemotherapy group.The main endpoints of this study were progression-free survival(PFS),objective remission rate(ORR)and disease control rate(DCR).The secondary endpoints were overall survival(OS)and toxicity.We used chi-square test or Fisher’s exact test to evaluated the differences of groups.Kaplan-Meier was used to build the survival curve.Using Cox proportional hazards regression model for prognostic factor analysis.All data analysis was carried out by SPSS 26.0.This study also collected peripheral blood cell counts,serum albumin(ALB)and lactate dehydrogenase(LDH).Neutrophil to white blood cell ratio(NWR),monocyte to white blood cell(MWR),lymphocyte to white blood cell(LWR),platelet to white blood cell(PWR),neutrophil to lymphocyte ratio(NLR),monocyte to lymphocyte ratio(MLR),platelet to lymphocyte ratio(PLR)and prognostic nutritional index(PNI)were calculated.The ROC curve was used to determined the cut-off values of nine indicators except LDH.According to the cut-off value,They were divided into baseline low-level and high-level groups and the survival differences were analyzed in groups.Result1.Compared with the chemotherapy group,the ORR of patients in bevacizumb combined with chemotherapy group was increased by 30.2%(P <0.001)and the DCR was increased by 11.4%(P=0.011).Besides,the medien PFS was extended 1.7months(P<0.001),and the median OS was extended 7.7 months(P=0.012)without increasing drug toxic effects.2.The cut-off values of NWR,LWR,MWR,PWR,NLR,MLR,PLR,ALB and PNI were 0.73,0.26,0.06,24.5,2.42,0.2,105,37.9 and 50.4,which were divided into baseline low-level and high-level groups.Univariate analysis revealed that baseline NWR(P=0.013),NLR(P=0.023),PNI(P=0.019),ALB(P=0.012)and LDH(P=0.037)were associated with PFS in advanced non-squamous NSCLC patients treated with bevacizumab and chemotherapy.The baseline LWR(P=0.044),NLR(P=0.014),MLR(P=0.011),PNI(P=0.002)were associated with OS.Multivariate analysis revealed that baseline NWR(P <0.001),PNI(P=0.022),ALB(P=0.047)and LDH(P=0.035)were independent prognostic factors for PFS in advanced non-squamous NSCLC patents treated with bevacizumab and chemotherapy.The baseline NLR(P=0.020)and PNI(P<0.001)were independent prognostic factors for OS.Conclusion1.In the real-world study,low-dose(7.5mg/kg)bevacizumab significantly improved the prognosis of driver gene-negative advanced non-squamous NSCLC patients without increased drug toxicity.2.Among patients with advanced non-squamous NSCLC treated with bevacizumab combined with chemotherapy,the higher NWR,LDH and lower ALB were independent risk factors for poor PFS;the higher NLR was an independent risk factor for poor OS,and the lower PNI was an independent risk factor for poor PFS and OS.Thus,baseline NWR,NLR,LDH,and PNI are independent prognostic predictors for patients with advanced non-squamous NSCLC treated with bevacizumab combined with chemotherapy.