Tki fa和ilure.pptVIP

Treatment strategy for EGFR-TKI failure patientsAdd on Chemotherapy Te-Chun, Hsia China Medical University Hospital Taichung, Taiwan Crossover Explains the Similar Survival RECIST Criteria What Happens at EGFR TKI Resistance in Patients with EGFR Mutation? What Happens at EGFR TKI Resistance in Patients with EGFR Mutation? Gefitinib Enhances Cytotoxicities of Antimicrotubule Agents in Non-Small-CellLung Cancer Cells Exhibiting No Sensitizing Epidermal Growth Factor ReceptorMutation. Tsai CM, Chiu CH, Chang KT, Chen JT, Lai CL, Chen YM, Hsiao SY. METHODS The combination effects of gefitinib with three antimicrotubule agents (AMTAs), paclitaxel,docetaxel or vinorelbine, or with gemcitabine were tested in 17 NSCLC cell lines Tetrazolium colorimetric assay and classical isobole method RESULTS Synergistic gefitinib/AMTA interactions were observed in the tested cell lines. The synergism was more robust in the four lines overexpressing de novo or acquired P-glycoprotein (Pgp; individual mCIs range, 0.484-0.859; all p values were 0.05), or in 12 cell lines exhibiting no sensitizing EGFR mutations (group mCIs for gefitinib/paclitaxel, gefitinib/docetaxel, and gefitinib/vinorelbine were 0.869, 0.82, and 0.853, respectively. All p values were 0.02). CONCLUSIONS Combined gefitinib/AMTAs showed synergism in NSCLC cells harboring no sensitizing EGFR mutations. Gefitinib could enhance AMTA effects through mechanisms not restricted to Pgp blockage. Interim analysis of afatinib monotherapy in patients with metastatic NSCLC progressing after chemotherapy and erlotinib/gefitinib in a trial of afatinib plus paclitaxel versus investigator’s choice chemotherapy following progression on afatinib monotherapy (lux-lung 5)  Martin Schuler, David Planchard, James Chih-Hsin Yang Study Design Efficacy Tumor response rate EGFR status Clinical enrichment criteria Result Median OS was 13.7 months in afatinib-treated patients Safety Diarrhea and rash/acne were the most frequentl