EGFR-TKI Combined With Ginsenoside Rg3 Compared With EGFR-TKI Alone In Patients With Advanced NSCLC: A Retrospective Study

Background and objectiveLung cancer is one of the most common malignant tumors in the world and causes high mortality,and non-small cell lung cancer(NSCLC)accounts for 85%.With the development of tumor molecular biology and genomics research,Epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)are currently recommended as the standard treatment for Non-small cell lung cancer(NSCLC)patients harboring epidermal growth factor receptor(EGFR)active mutation.According to the results of a number of randomized controlled clinical trials,EGFR-TKI has been recommended as the standard first-line treatment for advanced NSCLC patients with EGFR active mutation in the National Comprehensive Cancer Network(NCCN)guidelines.However,acquired drug resistance has become a big problem affecting the efficacy of EGFT-TKI.How to delay the EGFR-TKI drug resistance through combination therapy so as to give full play to the role of EGFR-TKI,is a hot and difficult point in the treatment of EGFR-TKI.Phase II clinical study(such as JO25567)showed that EGFR-TKI combined with anti-angiogenic drugs(Bevacizumab)can extend the effective time of EGFR-TKI.However,Bevacizumab is expensive and needs intravenous infusion,with high blood pressure,proteinuria,thrombosis and other adverse reactions.Ginsenoside Rg3 is a kind of domestic anti-angiogenic inhibitor which can down-regulate the expression of vascular endothelial growth factor(VEGF)and EGFR.Ginsenoside Rg3 has anti-angiogenic and anti-tumor effect.It is oral preparation,and the relative price is low,and the adverse reaction is mild.Ginsenoside Rg3 combined with EGFR-TKI could provide a new strategy to delay the EGFR-TKI resistance,and has therefore become a treatment of clinical prospects.This study explored the clinical benefit of NSCLC patients harboring EGFR active mutation of the Third Military Medical University affiliated hospital,and compared the efficacy and side effect of EGFR-TKI combined with ginsenoside Rg3 and EGFR-TKI alone,in the aim of providing a new therapeutic method for advanced NSCLC patients.Methods1.The medical data of patients diagnosed with advanced NSCLC with EGFR active mutation by cytology or histology in the affiliated hospitals of Third Military Medical University between January 2012 and January 2015 were retrospectively collected and analyzed.All of the patients were treated with first-line or second-line EGFR-TKI more than 2 months.The objective response rates(ORR),progression free survival(PFS),overall survival(OS)and side effect of the patients were observed and analyzed.2.Screening the the patients with first-line treatment to explore the synergistic effect of ginsenoside Rg3.All of them were divided into two groups A and B.Group A was test group,with patients taking EGFR-TKI and ginsenoside Rg3 at least 8 weeks;while group B was control group,with patients taking EGFR-TKI alone.PFS,OS,ORR and side effects of the two groups were analyzed.Results1.The data of 173 patients were collected.154 patients were treated with EGFR-TKI as first-line therapy and 19 patients were treated as second-line therapy.The median progression-free survival(mPFS)of first-line and second-line were 11.4 months and 10.0 months,respectively.The median overall survival(mOS)of first-line and second-line were 21.9 months and 19.3 months respectively.In addition,ORR of all the patients was 53.8%,and DCR was 98.8%.The ORR of first-line was 56.6%,and DCR was 99.3%.The ORR of second-line was 31.6%,and DCR was 94.3%.The 1-year survival rate of first-line patients was 90.1%,2-year survival rate was 46.4%,and 3-year survival rate was 17.3%.2.154 patients with first-line treatment were screened.30 patients taking ginsenoside Rg3 less than 8 weeks were excluded..The data of 124 patients were collected and analyzed.52 patients were in group A,and 72 patients were in group B.The ORR was higher in group A than in group B(59.6% vs 41.7%,P = 0.049).The m PFS in group A was 12.4 months,and that in group B was 9.9 months,a significant difference between the two groups(P = 0.017).When subgroup analyses were performed by baseline clinical characteristics in forest plot,patients in most subgroups including age ≤58,never smoking,ECOG PS 0-1,clinical stage IV,or administration of adenocarcinoma,gefitinib or icotinib,were treated with EGFR-TKIs plus ginsenoside Rg3,which could render better clinical outcome to their PFS.The m OS of group A showed no extended tendency compared with that of group B(25.4 months vs 21.4 months,P = 0.258).Rash was the worst side effect.Ginsenoside Rg3 did not significantly increase the side effect of EGFR-TKIConclusions1.EGFR-TKI could target advanced NSCLC patients harboring EGFR active mutation,and improve the ORR,PFS and OS.Then the side effects of it could be tolerated.Therefore,it can provide a powerful individual treatment for NSCLC.2.NSCLC patients with EGFR active mutation could obtain better PFS and ORR from EGFR-TKI combined with ginsenoside Rg3.Subgroup analyses showed that a variety of clinical characteristics have PFS advantages,and do not increase treatment-related side effects.3.Ginseoside Rg3 could enhance the efficacy of EGFR-TKI and delay the EGFR-TKI acquired resistance.Compared with other anti-angiogenesis drugs,ginseosied Rg3 has the advantages of cost-effectiveness,oral administration and good tolerance.The new strategy of ginseoside Rg3 combined with EGFR-TKI provides important clinical prospects,and lays the foundation for prospective controlled study.