Comparison Of Gefitinib Versus Adjuvant Chemotherapy In Patients With Stage ?-?A Non-small-cell Lung Cancer Harboring Positive EGFR Positive EGFR Mutations

BackgrougThe superior efficacy of first-line treatment with gefitinib over that of standard chemotherapy was demonstrated in patients with advanced non-small-cell lung cancer(NSCLC)harboring sensitive mutation of epidermal growth factor receptor(EGFR).However,scarce evidence showing the superiority of gefitinib to chemotherapy exists regarding the postoperative adjuvant therapy of EGFR mutation-positive patients with stage II to III A NSCLC.ObjectiveIn our study,we retrospectively reviewed a total of 116 patients with stage II to IIIA NSCLC harboring sensitive mutation of epidermal growth factor receptor(EGFR)who received gefitinib or adjuvant chemotherapy(AC),and analyzed the efficacy and safety profiles of the two groups.MethodsA total of 116 patients with completely resected ? to ?A NSCLC and confirmed positive EGFR mutation(exon 19 deletion or exon 21 Leu858Arg)between January 2013 and March 2017 were included in our study.DFS was analyzed in 55 patients(group A)treated with gefitinib and 61 patients(group B)treated with a platinum-based 2-drug combination AC.Propensity score matching(PSM)allowed the generation of best matched pairs for the two categories(1:1 ratio).The primary endpoint was disease-free survival(DFS).The second endpoint were overall survival(OS),the 2-year and 3-year DFS rate,adverse reactions.Factors affecting survival were assessed by the Kaplan-Meier method and Cox proportional hazard regression model.Results1.The matched cohort consisted of 52 gefitinib and 52 AC patients with the median follow-up of 37.1 and 31.5 months,respectively.DFS was significant longer in the gefitinib group than that in the AC group(34.9 months[95%CI,21.1-48.7]vs 19.3 months[95%Cl,13.3-25.3];(hazard ratio[HR],0.36;95%CI,0.19-0.68;Log-rank P=0.001).2.In the gefitinib group,the most common adverse events were rash(76.9%),aminotransferase elevation(53.8%)and diarrhea(46.2%),whereas in the AC group,the most common adverse events were neutropenia(67.3%),nausea or vomiting(63.5%)and anemia(44.2%)in AC group.Less frequentThe lower rate of grade = 3 adverse events was observed in the gefitinib group(15.4%versus 38,5%in the AC group).After receiving gefitinib for 3 months,one patient was diagnosed with interstitial lung disease which was regarded as the most severe treatment-related adverse event.3.The OS did not differ significantly between the gefitinib group and the AC group(HR,0.50;95%CI,0.18-1.40;Log-rank P=0.178).The 2-year and 3-year DFS rate were 75.0%and 44.0%,respectively,in the gefitinib group and 40%and 18%,respectively,in the AC group.4.The multivariate analysis showed that,in addition to the treatment group status,the number of positive lymph node stations was an significant factor for DFS.ConclusionIn our retrospective study,adjuvant gefitinib led to statistically significant DFS benefit compared with that for adjuvant chemotherapy in EGFR mutation-positive patients with resected ? to ?A NSCLC.Based on the superior DFS,reduced toxicity,and improved quality of life,adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients.However,this study did not provide an overall survival benefit in the adjuvant setting.These results will need further validation by prospective,randomized trials.