Retrospective Study Of EGFR-TKI Combined With Radiotherapy In Maintenance Therapy For Advanced Lung Adenocarcinoma Patients

ObjectiveEpidermal growth factor receptor(EGFR)is one of the most common driving genes of lung adenocarcinoma,and epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)has become the first-line therapy for patients with advanced lung adenocarcinoma.Compared with traditional chemoradiotherapy,although it has significant efficacy and less side effects,it is difficult to avoid the final outcome of drug resistance.To delay drug resistance,the most commonly used treatment strategy is EGFR-TKI combination therapy.EGFR-TKI can increase the sensitivity of radiotherapy,and radiotherapy can also reduce the probability of secondary drug resistance.Previous studies have shown that simultaneous EGFR-TKI combined with chest radiotherapy can prolong progression-free survival(PFS)compared with EGFR-TKI alone,however,adverse reactions of simultaneous EGFR-TKI combined with chest radiotherapy were also significantly increased.Maintenance therapy refers to a program of treatment with the same drug or drug change after a certain treatment to achieve the maximum effect of tumor control.Previous studies mainly focused on maintenance therapy after chemotherapy,but there are few studies on maintenance therapy after EGFR-TKI treatment.Therefore,this study aims to study the efficacy and safety of EGFR-TKI combined with chest radiotherapy as maintenance therapy compared with EGFR-TKI single-agent maintenance therapy in patients with advanced lung adenocarcinoma with EGFR-TKI mutation after disease stabilization,and to provide a new idea for clinical delay of acquired resistance to EGFR-TKI.MethodsClinical datas of patients with positive EGFR mutation who received first-line EGFR-TKI therapy and achieved disease stable and met inclusion and exclusion criteria were collected from Southwest Hospital of Army Military Medical University between January2013 and July 2019.Patients who underwent EGFR-TKI induction therapy to achieve disease stabilization and then maintained by thoracic radiotherapy were treated as the combined treatment group,maintained with monotherapeutic TKI were treated as the monotherapy group.Gender,age,ECOG PS score,smoking history,clinical stage,gene mutation type,first-line TKI medication,and craniocerebral metastasis were used as matching indexes,and SPSS software was used to make preference matching according to 1:2(combination therapy group: monotherapy group).The main outcome indicator was progression-free survival(PFS).Secondary efficacy indicators were Duration of response(DOR),Objective response rate(ORR),and Disease control rate(DCR).The safety index was adverse event(AE)and its incidence.Other indicators included the optimal percentage of change in target lesion size from baseline,and PFS subgroup analysis for each clinical feature.Results1.A total of 178 patients meeting the criteria were collected,including 23 patients in the combined treatment group and 155 patients in the single-agent treatment group.After Propensity score matching(PSM)1:2,23 patients in the combined treatment group and 46 patients in the single-agent group were obtained.The baseline level of all clinical characteristics of the two groups was the same(P> 0.05).2.Median PFS was 19.8 months(95%CI 16.7-22.9 months)and 12.2 months(95%CI11.5-13.0 months)in the combination therapy group and the monotherapy group,with HR=0.47(95%CI 0.29-0.77),p =0.000,and the difference was statistically significant.The median DOR of the two groups was 16.4 months(95%CI 15.7-17.1 months)and 10 months(95%CI 8.2-11.8 months),respectively,with HR=0.39(95%CI 0.22-0.69),p =0.001,showing a statistically significant difference.ORR in combination group was 86.9%,single-agent group was 67.4%(p =0.081)and there is no difference between two groups.DCR was 100% in both groups.3.The optimal percentage of target lesion size change from baseline in the two groups was(44.2±12.8)% and(36.8±18.3)%,t=1.724,p =0.089,respectively,and the difference was not statistically significant.4.In the PFS subgroup analysis for each clinical feature,the p values of the subgroups≤60 years old,> 60 years old,male,female,non-smoking,ECOG PS 0 score,IVA/B stage,EGFR19 deletion,gefitinib,erlotinib,and no brain metastasis were all less than 0.05,that is,the combination group had better PFS benefits than the single drug group in the above subgroups.5.Grade 3 and above adverse reactions were found in 6 cases(26.1%)and 10 cases(21.7%),respectively.There was no significant difference in common adverse reactions between the two groups.The most common adverse reactions were rash(10 cases(43.5%)and 21 cases(45.7%),respectively).Radiation pneumonia occurred in 11 patients(47.8%)in the combination therapy group,including 9 cases of grade 1 and 2 case of grade 2,all patients with radiation pneumonia improved with appropriate treatment.ConclusionAfter first-line EGFR-TKI induction therapy,EGFR-TKI combined with thoracic radiotherapy maintenance therapy showed better PFS and DOR benefit than EGFR-TKI single-drug maintenance therapy and the combination therapy group had a safety tolerance.This study provides a new way to delay the acquired resistance of EGFR-TKI clinically,and can be considered as an alternative treatment for patients with advanced lung adenocarcinoma with EGFR-mutation positive.