Abstract
BackgroundThe third generation Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) osimertinib has been initially approved for T790M positive lung adenocarcinoma patients and more recently for first-line treatment of EGFR-mutant T790M negative lung adenocarcinoma, Similarly to previous generation TKIs, despite the high response rate, disease progression eventually occurs and current clinical research is focused on novel strategies to delay the emergence of osimertinib resistance.In this study,we investigated a the combination of osimertinib/ gefitinib/ erlotinib with cytotoxic chemotherapy for EGFR-mutated positive lung adenocarcinoma patients in long-term survival outcomes. Method We enrolled Ⅲb-IV stage lung adenocarcinoma patients with an EGFR mutation，Patients receiving standard Osimertinib,Gefitinib,Erlotinip alone treatment and Osimertinib,Gefitinib and Erlotinip with cytotoxic chemotherapy treatment were retrospectively reviewed.The performance status were collected,The response rate, progression-free survival (PFS) and overall survival (OS) and toxicity profile were analyzed.ResultBetween January 2014 to Dec 2020,240 patients with Ⅲb-Ⅳstages lung adenocarcinoma were enrolled from a institution.All patients who received different standard treatment respectively,were divided into four groups,64 who received（gefitinib or Erlotinb)with cytotoxic chemotherapy, 60 who received single gefitinib or erlotinib.58 who received (Osimertinib) with cytotoxic chemotherapy,58 who received single (Osimertinib) were eligible for this study.First generation Chemical-TKItherapy group PFS vs First generation TKI therapy alone PFS.P<0.05. Mean Survival Time 22.00 month,95%CI[16.29,27.70] VS 16.00 month.95%CI[11.98,20.01].First generation Chemical-TKItherapy group OS vs First generation TKI therapy alone OS. P<0.05. Mean Survival Time 32.00 month,95%CI[25.29,3871] VS 28.00 month, 95%CI[14.58,41.41].Third generation Chemical-TKItherapy group PFS vs Third generation TKI therapy PFS. P<0.001.Mean Survival Time 40.00,95%CI[28.12,51.87] VS 26.66 95%CI[24.77,29.22].Third generation Chemical-TKItherapy group OS vs Third generation TKI therapy OS.P<0.05. Mean Survival Time 48.00.95%CI[42.81,53.18] VS 36.00. 95%CI[34.71,38.28].First-Third generation Chemical-TKItherapy group PFS vs.First-Third generation TKI therapy alone PFS.P<0.001.Mean Survival Time 28.00,95%CI[24.86,31.11] VS 17.00 95%CI[13.83,20.16].First-Third generation Chemical-TKItherapy group OS vs First-Third generation TKI therapy alone OS.P<0.001. Mean Survival Time 41.00.95%CI[31.70,50.30] VS 29.00. 95%CI[17.68,38.31].Cox regression models showed a significant prognostic factors for OS were old age (55-69 years) (HR = 0.49 [0.28–0.89], p < 0.02) and gene mutation (Positive) (HR = 0.15 [0.07–0.29], p < 0.05),First add third generationTKI with chemicaltherapy (HR = 0.56 [0.35–0.89], p < 0.02). ConclusionFirst-Third generation EGFR inhibitor combined with cytotoxic chemotherapy represents a suitable palliative treatment option in further therapy lines for elderly patients with advanced lung adenocarcinoma.The results obtained under real-life conditions add to our understanding of the benefits and risks of First-Third generation EGFR inhibitor combined with cytotoxic chemotherapy in routine clinical practice.
Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance
