Clinical Study Of Apatinib Plus EGFR-TKI In Treating Advanced NSCLC After EGFR-TKI Treatment Slow Progression

Objective:Lung cancer is one of the leading causes of cancer-related causes of death.Non-small cell lung cancer(NSCLC)accounts for 85% of lung cancer.Most patients have already been found in stage IIIB-IV when they are diagnosed,and require systemic therapy.About 50% of Chinese patients with advanced NSCLC have mutations of the Epidermal Growth Factor Receptor(EGFR)gene,including exon 19 non-frameshift deletion and L858 R point mutation in exon 21,Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI)has become the first-line standard treatment for this type of patients,but due to the different degrees of acquired resistance,the median Progression-Free Survival(PFS)is about 10-16 months.To solve this problem,scholars have tried a variety of new treatments to reverse resistance,thereby improving efficacy.These include antagonizing new mutations,finding new targets,and using EGFR-TKI in combination with other treatments such as TKI and chemotherapy alternate use,TKI combined with chemotherapy,TKI combined with anti-angiogenic drugs,and TKI combined with immunotherapy.Apatinib is an oral anti-angiogenic drug independently developed in China.Its molecular weight is small,and it can preferentially interact with the Vascular Endothelial Growth Factor Receptor 2(VEGFR-2)kinase region.The high affinity binding of the ATP binding site results in the inactivation of VEGFR-2,blocking downstream signaling,inhibiting tumor angiogenesis,and achieving anti-tumor effects..Many clinical trials have shown that EGFR-TKI combined with anti-angiogenic drugs can prolong the resistance time of EGFR-TKI.Therefore,we conducted a retrospective study of patients with advanced NSCLC who progressed slowly after the first generation of EGFR-TKI treatment to explore the efficacy and safety of EGFR-TKI prodrug maintenance combined with apatinib.The exploration of prodrug maintenance combined with Apatinib.Research Method:The 30 cases were selected from the patients the Department of Oncology in the Second Hospital of Dalian Medical University from September 1st,2016 to July 1st,2018.They were treated by the first generation EGFR-TKI treatment,slowly progressed,and continued the maintenance of the original drug was continued with Apatinib.In the case of patients with advanced NSCLC,1 patient was excluded from the primary liver cancer,the actual enrollment of 29 patients,consistent with the definition of slow progression(disease control ?6 months,compared with the previous assessment,the tumor load was slightly increased by ?2 points,symptom score ?1 point),the enrolled patients continued to maintain the original drug dose combined with oral apatinib 250 mg / day as the initial dose until the progression of disease,unacceptable toxicity,or the doctor / patient decided to stop treatment.According to the evaluation criteria of the solid tumor evaluation system(Response Evaluation Criteria In Solid Tumors,RECIST1.1),we assess the recent research,and analyze the Objective Response Rate(ORR),Disease Control Rate(DCR),and median Progression-Free Survival(PFS),median Overall Survival(OS),and adverse events.Analysis by SPSS24.0 software: The clinicopathological features of the patients were described by percentage(%),the survival curve was drawn by Kaplan-Meier method,and the relationship between clinical pathological features and PFS were analyzed by Log-rank method.P<0.05 indicates that the difference is statistically significant.Research Results:During the follow-up period to January 1st,2019,7 of 29 patients died,without achieving the median OS;median PFS was 5.470 months(95% CI 4.367-6.573 months);4 enrolled patients reached PR,no case of CR,ORR was 13.8%(4/29);21 cases of SD,disease control rate was 86.2%(25/29);15 patients received combination therapy for second-line treatment,ORR and DCR respectively For 20%(3/15)and 80%(12/15),14 patients received third-line and above treatments,with ORR and DCR being 7.1%(1/14)and 92.9%(13/14),respectively.Common drug-related toxicities were hypertension,fatigue,and proteinuria,which accounted for 55.2%(16/29),34.5%(10/29),and 24.1%(7/29),respectively.4 patients who clinical symptoms are stable and increased lesions after a combination of treatment for a period of time,but did not reach the progress of the disease,did not change other treatment options,the dose of apatinib was added to 500 mg / day,the lesions stabilized or reduced again.Among the EGFR-sensitive mutations,the median PFS of the L858 R point mutation patients was significantly longer than that of the 19 th exon non-frameshift patients,and the difference was statistically significant(P=0.011).Conclusions: 1.Advanced NSCLC patients who progress slowly after EGFR-TKI treatment are effective in combination with apatinib,which can prolong the use of the first generation EGFR-TKI and may potentially prolong the overall survival of patients.2.The toxic and side effects of the first generation EGFR-TKI combined with apatinib are controllable,and the patients' compliance is good.3.Patients with L858 R point mutations may benefit from the first generation EGFR-TKI in combination with apatinib compared with 19 th exon nonframeshift patients.4.In patients with a benefit of a combination of EGFR-TKI and apatinib,when the clinical symptoms are stable and the lesions increase,but the disease progression is not achieved,increasing the dose of apatinib may delay the drug resistance time again.