Clinical Efficacy And Safety Of Apatinib Combined With Chemotherapy In The Second-line Treatment Of Small Cell Lung Cancer

Background and objective:Small cell lung cancer（SCLC）is a highly aggressive neuroendocrine tumor with a high degree of malignancy and rapid proliferation,accounting for about 15% of all lung cancers.Although SCLC is sensitive to first-line therapy such as etoposide combined with platinum,most patients have a high probability of recurrence after firstline therapy and are prone to distant metastasis.Therefore,prolonging the survival period of patients and improving the quality of life of patients have become the primary issues in the second-line treatment of SCLC.Apatinib is a small molecule oral tyrosine kinase inhibitor independently developed in our country.Its main mechanism is to specifically inhibit vascular endothelial growth factor receptor-2（VEGFR-2）,inhibit tumor the formation of new nourishing blood vessels,thereby inhibiting tumor growth and metastasis.As a new anti-angiogenic drug,a large number of studies have shown that apatinib alone has good clinical efficacy in patients with SCLC,but the report of apatinib combined with chemotherapy on SCLC is inconclusive,and further research is still needed.Our objective is to evaluate the clinical efficacy and safety of apatinib combined with chemotherapy in the second-line treatment of SCLC.Methods:This study included patients with advanced SCLC who relapsed after first-line treatment in the Cancer Center of the First Hospital of Jilin University.All patients were initially given oral apatinib 500 mg/d combined with 4 cycles of standard second-line chemotherapy,and continued apatinib single-agent maintenance therapy after chemotherapy until disease progression or intolerable side effects.However,most of the patients we enrolled at the beginning of the trial had dose reductions because they could not tolerate 500 mg/d of apatinib,so the initial dose of apatinib was adjusted to250 mg/d in subsequent patients.During the course of treatment,if the patient develops intolerable side effects,the dose of apatinib can be reduced to 250 mg/qod orally.The primary endpoint of this study is progress free survival（PFS）,and the secondary endpoints are objective response rate（ORR）,disease control rate（DCR）,overall survival（OS）and adverse event（AE）.The RECIST1.1 solid tumor curative effect evaluation standard was used to evaluate the curative effect,the SPSS 26.0 software was used for statistical data analysis,and the Kaplan-Meier method was used to analyze the survival trend.Results:We have previously reported data on patients with an initial dose of 500 mg/d of apatinib,so this article only presents the results of this study of patients with an initial dose of 250 mg/d of apatinib.From August 15,2018 to October 25,2019,a total of 13 patients were included in this trial,all of whom were second-line treatment,and 11 of them could be evaluated for efficacy.Among the patients who could be evaluated for tumor response,0 had complete response（CR）,3 had partial response（PR）,7 had stable disease（SD）,and 7 had progressive disease（PD）was 1 case.The overall ORR and DCR were 27.27%（3/11）and 90.91%（10/11）,respectively.As of June 1,2021,1patient was still in the group,10 patients were withdrawn because of PD,1 patient was withdrawn because of intolerance,and 1 patient was withdrawn because of death.Of the 12 patients who were enrolled,7 received subsequent chemotherapy and 5 did not.Overall patients had a median PFS of 7.43 months and a median OS of 14.88 months.In terms of safety,the most common adverse event（AE）was anemia（30.77%,4/13）,followed by neutropenia（23.08%,3/13）and leukopenia（23.08%,3/13）/13).Grade 3-4 adverse events were neutropenia（7.69%）,leukopenia（7.69%）and diarrhea（7.69%）.Apatinib-related AEs such as hypertension,proteinuria,and hand-foot syndrome were also reported in this study,but the incidence was low and did not reach grades 3-4.In terms of dose usage,most of the patients were safe and tolerable,and only 2 patients were reduced from 250 mg/qd to 250 mg/qod,and no additional toxic and side effects were found.Conclusion:1.Compared with second-line chemotherapy alone,apatinib combined with single-agent chemotherapy had a good effect on the second-line treatment of SCLC,with a median PFS of 7.43 months and a median OS of 14.88 months,and the safety was tolerable.2.The incidence of adverse events related to low-dose apatinib treatment is relatively low.In the treatment of second-line SCLC,apatinib 250 mg/d may be a potential treatment option as a safe dose of combination chemotherapy,but it still needs to be confirmed by studies with a larger sample size.