Docetaxel Plus Platinum Versus Pemetrexed Plus Platinum As Subsequent Treatment Of Advanced Lung Adenocarcinoma With Acquired Resistance To EGFR-TKI,Gefitinib

Introduction Lung cancer is the leading cause of cancer-related mortality in China.EGFR are overexpressed in 40-80% of lung adenocarcinoma and in those cases,EGFR-TKIs are effective as first line treatment.Despite the clinical benefit provided in adenocarcinoma carriers of EGFR mutations when treated with TKIs,a large number of these patients will eventually develop disease progression.Patients with activating EGFR mutations who progress on EGFR-TKIs and those with unknown mutation status who have a prolonged response to EGFR-TKIs(>6 months)and then progress are classified as having acquired resistance and will require second line therapy.Docetaxel and Pemetrexed are such alternatives as second line treatment drugs and when given in combination with a platinum compound,are known to have better efficacy.Objectives We aimed to retrospectively compare the efficacy and survival of two regimens: docetaxel in combination with a platinum compound and pemetrexed in combination with a platinum compound,as subsequent treatment following acquired resistance to first line therapy with EGFR-TKI,gefitinib in patients with advanced lung adenocarcinoma.Materials and methods We retrospectively analyzed 56 Chinese patients at the First Affiliated Hospital of Zhengzhou University,above the age of 30 years(19 males and 37 females)all diagnosed with advanced lung adenocarcinoma who eventually developed resistance to the EGFR-TKI,gefitinib,either alone or in combination with chemotherapy,as first line treatment.As subsequent treatment,28 patients received docetaxel in combination with a platinum compound while the remaining 28 patients received pemetrexed in combination with a platinum compound.Clinical parameters including age,gender,smoking history,performance status,stage of disease,patho-morphological diagnosis,type of EGFR mutation,T790M mutation status,mean tumor volume change,development of new metastases and side effects that entailed after the different regimens were all recorded.Efficacy was assessed according to the RECIST Version 1.1 criteria and treatment toxicity was assessed by CTC scale.Performance status was evaluated according to ECOG scale.We performed statistical analysis using SPSS Version 21.0(SPSS Inc.,Chicago,IL,USA).Results All patients were tested for EGFR mutation;out of which 66.1% had deletions in exon 19 and 33.9% had point mutation in exon 21.The median age of was 55 years.Females accounted for 66.1% and males 33.9%.85.7% were non-smokers and 14.3% were smokers.75% were positive for T790 M mutation.There was no patient with complete response(CR).In the docetaxel arm,7 PR(46.4%),10 SD(35.7%)and 5 PD(17.9%)cases were recorded and in the pemetrexed arm,16 PR(57.1%),0 SD and 12 PD(42.9%)cases were recorded.The objective response rates were 46.4% and 57.1% in the docetaxel and pemetrexed groups respectively.The median PFS for all the 56 patients after EGFR-TKI failure was 3.800 months(95% CI = 3.506 – 4.094).The median PFS for patients who received docetaxel with a platinum compound was 3.300 months(95% CI = 2.950 – 3.650)and for those who received pemetrexed with a platinum compound was 4.1 months(95% CI = 3.893 – 4.307).The median OS of all the 56 patients after EGFR-TKI failure was 9.00 months(95% CI = 8.645 – 9.355).The median OS for patients who received docetaxel with a platinum compound was 7.90 months(95% CI = 6.453 – 9.347)and for those who received pemetrexed with a platinum compound was 10.00 months(95% CI = 9.156 – 10.844).The difference in both PFS and OS between the two groups was significant(p < 0.005).Conclusion In cases of advanced lung adenocarcinoma with acquired resistance to the EGFR-TKI,gefitinib,the combination of pemetrexed with a platinum compound is a comparatively superior treatment regimen in terms of both efficacy and survival.