| Objective: The association between the depth of response(DoR)of first-line targeted therapy and the prognosis of patients with advanced lung adenocarcinoma with EGFR-sensitive mutations remains controversial.The study aims to explore the influence of DoR on the overall survival(OS)and progressionfree survival(PFS)of patients with advanced lung adenocarcinoma who are treated with targeted therapy in the first line.Methods: 215 advanced lung adenocarcinoma patients harboring EGFR driver mutation(exon 19 deletion or 21L858R)admitted to the Affiliated Tumor Hospital of Guangxi Medical University from January 1,2013 to December 31,2019 were retrospectively included for analysis.All patients received firstgeneration EGFR tyrosine kinase inhibitors(TKIs)icotinib or gefitinib as the first-line targeted therapy.Target lesions of tumor were selected according to RECIST1.1,and the percentage of the maximum shrinkage of the target lesions was calculated compared with the baseline.Non-target lesions and new lesions were not included when calculating the DoR.The patients with non-tumor shrinkage were the control group,and the tumor remission> 0% was divided into1-25%,26-50%,51-75%,76-100%.The smooth curve fitting was used to observe the linear relationship between DoR and the risk of death of advanced lung adenocarcinoma after adjusting for confounding factors.The multivariate COX proportional hazard regression model was used to evaluate the independent effects of DoR on OS and PFS of advanced lung adenocarcinoma with EGFR sensitive mutations,and the trend test were performed.We use stratified analysis to understand the impact of different DoR on OS in different populations,and conduct trend test and interaction test.Survival curves were estimated using the Kaplan-Meier method.Results: A total of 215 patients with advanced lung adenocarcinoma harboring EGFR mutation(exon 19 deletion or 21L858R)were included.As of the last follow-up date,130 patients(60.47%)died,and 199 patients(92.56%)had disease progression.There were 20 patients(9.30%),44 patients(20.47%),82 patients(38.14%),56 patients(26.05%),and 13 patients(6.05%)in the groups of DoR ≤0%,1-25%,26-50%,52-75%,and 76-100%.The univariate COX model showed that baseline serum albumin,adrenal metastasis and DoR were the influencing factors of the risk of death of advanced lung adenocarcinoma(p<0.05).The smooth curve fitting showed that the DoR has a linear relationship with the risk of death of advanced lung adenocarcinoma after adjusting for confounding factors.The multivariate Cox proportional hazards model showed that compared with DoR≤0%,the risk of death in the DoR 1-25%,26-50%,51-75%,and 76-100%decreased by 41% [hazard ratio(HR): 0.59,95% confidence interval(CI): 0.29-1.18,p=0.1341],64%(HR: 0.36,95%CI: 0.18-0.71,p=0.0029),77%(HR: 0.23,95%CI: 0.11-0.49,p=0.0001),90%(HR: 0.10,95%CI: 0.04-0.29,p<0.0001),respectively.The trend test showed that compared with DoR≤0%,for every 25%increase in DoR,the risk of death of lung cancer decreased by 40%(p for trend<0.0001),which was a stepwise decrease.The median OS in the group of DoR≤0%,1-25%,26-50%,51-75%,and 76-100% were 11.33,21.70,28.67,29.40,36.67 months,respectively(log-rank p<0.0001).In the univariate COX proportional hazard model,adrenal metastasis and DoR were the influencing factors of PFS(p<0.05).After adjusting for confounding factors,compared with DoR≤0%,the risk of disease progression in DoR1-25%,26-50%,51-75%,and76-100% decreased by 60%(HR: 0.40,95% CI: 0.21-0.74,p=0.0038),67%(HR:0.33,95%CI: 0.18-0.58,p=0.0001),71%(HR: 0.29,95%CI: 0.15-0.53,p<0.0001),82%(HR: 0.18,95%CI: 0.08-0.40,p<0.0001).Trend test showed that for every 25% increase in DoR,the risk of disease progression decreased by 27%(p for trend<0.0001).The median PFS in the group of DoR≤0%,1-25%,26-50%,51-75%,and 76-100% were 1.97,9.39,10.62,11.40,and 17.90 months,respectively(log-rank p<0.0001).Conclusion: 1.In patients with advanced lung adenocarcinoma harboring EGFR mutation(exon 19 deletion or 21L858R)who received EGFR-TKIs as first line treatment,DoR is negatively correlated with the risk of death and disease progression.For every 25% increase in DoR,the risk of death decreases by 40%and the risk of disease progression decreases by 27%.2.DoR is significantly related with OS and PFS in patients with advanced lung adenocarcinoma with EGFR mutations,indicating that it may be an important prognostic indicator for efficacy evaluation of first-line targeted therapy in such patients.3.The OS and PFS of patients with DoR>75% are significantly prolonged,which can further stratify the partial response population of advanced lung cancer and is expected to become a supplement to RECIST. |
