Sequential TKI In Combination With Chemotherapy In The Treatment Of Advanced Non-small Cell Lung Cancer With Acquired Tyrosine Kinase Inhibitor Resistance

Background:Advanced non-small cell lung cancer(NSCLC) is the leading cause of cancer-related death. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) emerges as an effective therapy for NSCLC following chemotherapy. Some patients showed initial response to EGFR-TKI, however, ultimately developed resistance to these agents. Presently, there is no standard treatment after acquired resistance to EGFR-TKI. The lack of established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKI treatment poses a great challenge to physicians and oncologists..Objective:To evaluate the efficacy and safety of sequential administration of TKI and chemotherapy on the advanced non-small cell lung cancer patients after acquired resistance to TKI treatment and study the relationship of efficacy and clinical characteristics.Methods:We did a retrospective analysis of advanced NSCLC patients who previously had disease control with either gefitinib250mg or erlotinib150mg daily and showed progression from April2007to December2012. After acquired TKI resistance was confirmed according to the criteria established by Jackman, patients received subsequent chemotherapy with a nab-paclitaxel/platinum combination regimen until disease progression or intolerable toxicity. The efficacy, side effects and the relationship between efficacy and clinical characteristics were observed.Results:A total of21NSCLC patients were enrolled in this study. Among twenty-one patients, three had partial response and eleven had a stable disease, resulting in an objective response rate (ORR) of14.3%and a disease control rate (DCR) of66.7%. The patients who had obtained disease control with sequential regimen, showed a longer time to progression (200vs.101days, P=0.004). Thirteen patients had tumors with known EGFR mutation status, seven had sensitive EGFR mutations and six had wild-type EGFR Patients who had sensitive EGFR mutation exhibited higher disease control rate and median time to progress (71.4%and234days,) respectively than patients had wild-type EGFR(50.0%and90days) respectively. There was no difference in time to progression administered to patients in second-line sequential regimen compared with those in third-line treatment. The most common toxic effects were skin rash, diarrhea and hematologic toxicity.Conclusion:Sequential administration of EGFR-TKI and chemotherapy with a nab-paclitaxel/platinum combination regimen seems to be effective in patients with advanced NSCLC after acquired EGFR-TKI resistance.