Individualized Therapy Of Advanced Non-small Cell Lung Cancer With Acquired Resistance To Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Background: Targeted therapy has become an effective means of treatments foradvanced non-small lung cancer. Epidermal growth factor receptor tyrosine kinaseinhibitors made significant advances in the treatment of sensitive EGFR mutation inNSCLC patients. However, resistance to EGFR-TKIs inevitably occur. Acquired resistancebecomes a clinical challenge to be resolved urgently.Objective: To evaluate the significance of different treatment methods betweenindividualized therapy and best supportive care (BSC) on the advanced non-small celllung.Methods: From January2012to April2014, we did a retrospective analysis ofadvanced NSCLC patients who previously had disease control with either gefitinib250mgor erlotinib150mg daily and showed progression afterwards. Once acquired TKIresistance was confirmed according to the criteria established by Jackman, differenttreatment strategies were adopted according the pattern of progession. Thirty-four patientsreceived individualized therapy (including chemotherapy, local therapy and continuation ofTKIs) in contrast to16patients received BSC. We evaluated therapeutic effect according toRECIST (version1.1) standard and compared the survival difference between two groupsby Kaplan-Meier survival analysis.Results: A total of50NSCLC patients were enrolled in this study. Of the50patients,thirty-four patients received individualized therapy. Among them,6shows partialremission,19achieved stable disease,9experienced progressive disease. The diseasecontrol rate (DCR) was66.7%. The median PFS was4.2(1.1~14.4) months. Sixteen patients received best supportive care. At the same time, survival analysis showedsignificant difference between individualized therapy and supportive care groups (33.4vs.20.4months, X2=7.266, P=0.007). Thirteen cases with local progression received localtreatment combined with EGFR-TKIs, the median PFS was4.5(1.3~14.4) months, with alonger OS compared with6cases with the same progression pattern adopted best supporttreatment (38.4vs.17.3months, X2=9.913, P=0.002). The median PFS of dramaticprogression and gradual progression were6.7(1.3~10.4) months and3.3(1.1~5.2) monthsrespectively. Overall survival analysis showed no significant difference betweenindividualized therapy and supportive care groups.Conclusion: Individualized therapy according to progression pattern seems to beeffective in patients with advanced NSCLC after acquired EGFR-TKI resistance.