Clinical Observation Of EGFR-TKIs Combined With WBRT Versus EGFR-TKIs Alone In The Treatment Of Patients With EGFR-sensitive Mutant Lung Adenocarcinoma With Inital Brain Metastases

Background and Objective: For patients with non-small-cell lung cancer(NSCLC)and multiple brain metastases,whole brain radiotherapy(WBRT)is a standard-of-care treatment,but it eff ects on memory and cognitive function.EGFR-tyrosine kinase inhibitors(EGFR-TKIs)is the standard treatment for advanced NSCLC harboring EGFR mutations,which is also effective for brain metastases.However,whether EGFR-TKIs plus WBRT is superior to EGFR-TKIs alone for the treatment of advanced EGFR-mutant lung adenocarcinoma with brain metastases remains controversial.This study aimed to investigate the efficacy and prognosis of concurrent EGFR-TKIs and WBRT versus EGFR-TKI alone in a retrospective cohort of advanced EGFR-mutant lung adenocarcinoma with brain metastases,and to provide reference for the treatment of such patients.Methods: A total of 75 lung adenocarcinoma patients with EGFR sensitive mutant and initial brain metastases were included in Affiliated Tumor Hospital of Guangxi Medical University from February 22,2012 to April 27,2018.The clinical data was retrospectively analyzed and summarized.Patients were divided into EGFR-TKIs combined with WBRT group and EGFR-TKIs alone group.The primary endpoint were intracranial objective response rate(iORR),intracranial disease control rate(iDCR)and Intracranial progression-free survival(iPFS).The secondary were progression-free survival(PFS),overall survival(OS).The median follow-up time was 20.8 months.SPSS21.0 software was applied for Statistical analysis.?2 test and continuous correction was used for differences survival between groups.Kaplan-Meier method was used for survival analysis,and Log-rank test was performed.A Cox proportional hazard model was used to analyze iPFS and OS.All statistical results were considered statistically significant at p?0.05.Results:1.The iORR of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were 72.7% and 75.5%,respectively.No statistical difference was found between two group(?2=0.062,p=0.804).The iDCR of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were 95.5%and 98.1%,respectively.No statistical difference was found between two group(?2=0.000,p=1.000).2.The median iPFS of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were 18.3 months(95% CI: 8.6~28.0)and 15.6 months(95% CI: 9.9~21.3),respectively,and the difference was not statistically significant(?2=0.986,p =0.321).3.The median iPFS of ECOG PS 0~1 and ECOG PS 2~3 patients were17.0 months(95% CI: 11.8 to 22.2)and 9.7 months(95% CI: 0.8 to 18.6),respectively,the difference was statistically significant(?2=7.379,p=0.007).Subgroup analysis showed that for patients with ECOG PS 0~1,the median iPFS of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were25.4 months(95%CI: 17.1~33.7)and 14.9 months(95%CI:9.2~20.6),the difference was statistically significant(? 2=4.204,p=0.04).However,for patients with ECOG PS 2~3,the median iPFS of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were 9.3 months(95%CI: 5.7~12.9)and16.5 months(95%CI:0.0~35.3),the difference was not statistically significant(?2=0.655,p=0.418).4.The median PFS of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were 10.5 months(95% CI: 4.6~16.4)and 9.2 months(95%CI:8.0~10.4),respectively,and the difference was not statistically significant(?2=3.824,p =0.051).5.The median OS of EGFR-TKIs combined with WBRT group and EGFR-TKIs group were 23.7 months(95% CI: 4.9~42.5)and 23.1 months(95% CI:16.4~29.8),respectively,and the difference was not statistically significant(?2=0.280,p =0.596).6.In multivariate Cox analysis,ECOG PS 0~1 was significant independent prognostic factor for iPFS in lung adenocarcinoma with brain metastases(p=0.013).However,multivariate Cox analysis did not find independent prognostic factors for OS(p>0.05).Conclusion:1.For patients with EGFR sensitive mutations lung adenocarcinoma and brain metastases.Adding WBRT to EGFR-TKIs failed to improve iORR and iDCR,and did not prolong iPFS,PFS and OS.2.For patients with ECOG PS 0~1,EGFR-TKIs combined with WBRT may be a better choice.3.ECOG PS 0~1 was significant independent prognostic factor for iPFS of advanced EGFR-mutant lung adenocarcinoma with brain metastases.