Abstract: ObjectiveTo investigate the efficacy of different regimens in patients with anaplasticlymphoma kinase （ALK） fusion genepositive pulmonary adenocarcinoma of a cquired crizotinib resistance. 
MethodsFrom January 2014 to October 2017， 65 patients with advanced ALK fusion genepositive pulmonary adenocarcinoma of acquired crizotinib resistance in our hospital were enrolled. According to the treatment regimes， 13 cases received ALK inhibitors and remaining 52 cases received systemic chemotherapy， including 23 cases of pemetrexed plus platinum， 10 cases of paclitaxel plus platinum， 3 cases of vinorelbine and platinum， 5 cases of gemcitabine and platinum， 5 cases of pemetrexed alone and 6 cases of docetaxel alone. After 2 cycles， the efficacy and adverse reactions were evaluated by RECIST 11 and NCICTC 40， and the prognosis of different treatment schemes was analyzed according to the followup data. 
ResultsAll patients were evaluable for efficacy with the objective response rate （ORR） of 462％ and the disease control rate （DCR） of 738％. Patints receiving the second generation of ALK inhibitor showed better RR than cytotoxic drugs （769％ vs. 385％， P=0013）. For chemotherapy group， pemetrexedcontained regimens had better RR than nonpemetrexed regimens （536％ vs. 208％， P=0016）， and platinumcontained regimens were better than monotherapy in DCR （805％ vs.364％，P=0013）. The progression free survival（PFS）and overall survival （OS） of all patients were 40 months（95％CI： 3248）and 190 months（95％CI： 174206）, respectively. The second generation of ALK inhibitor was better than cytotoxic drugs for PFS （100 months vs. 40 months，P=0003） and OS （250 months vs.185 months， P=0012）. ECOG 01 （195 months vs.170 months，P=0004） and clinical stage ⅢB were favorite factors for OS （265 months vs. 185 months， P=0046） comparing with ECOG 2 and stage Ⅳ， respectively. 
ConclusionThe second generation of ALK inhibitor presented stronger efficacy in ALKfusiongene positve pulmonary adenocarcinoma patients after the failure of crizotinib. ECOG 01 and phase ⅢB patients had longer OS.

Key words: Pulmonary adenocarcinoma, Anaplastic lymphoma kinase（ALK）, Chemotherapy, Drug resistance