Clinical Efficacy Of Crizotinib Therapy In ALK-positive Advanced Non-small Cell Lung Cancer

Objectives1.To collect the baseline information of all qualified patients and analyze the clinical baseline characteristics of patients with ALK-positive advanced non-small cell lung cancer.2.To analyze the clinical efficacy of Crizotinib in the treatment of patients with ALK-positive advanced NSCLC,and to explore the influencing factors.3.To observe the safety of Crizotinib in the treatment of ALK-positive NSCLC patients.4.To analyze the Crizotinib resistance pattern,and the clinical efficacy of taking second-generation and third-generation ALK inhibitors,Crizotinib beyond disease progression after Crizotinib resistance.MethodsWe collected the cases of all ALK-positive NSCLC patients who were administrated with Crizotinib in the Zhejiang Cancer Hospital from 2013-04-01 to 2019-02-01.The data included: 1.Baseline information: gender,age,smoking status,smoking index,clinical stage,tumor metastasis site,gene mutation,etc;2.Treatment information: medication regimen,adverse drug reactions,treatment after drug resistance,etc;3.Prognostic information: the efficacy and survival time of Crizotinib and second-and third-generation ALK-TKI.After the data had been collected,consolidated,all data were statistically analyzed by SPSS 22.0.Results1.There were 227 patients with ALK-positive advanced NSCLC in this study,with slightly more females.The age range was 23-82 years.Two-thirds patients had no history of smoking.The clinicopathologic type of patients was adenocarcinoma(96%).91.2% of the patients were diagnosed with stage IV.The common distant metastases sites were brain,bone,etc.There were13 patients with ROS1 fusion and 7 patients with c-Met amplification.The ECOG PS score was0-1 in 85.5% of patients.2.The overall,first-line and non-first-line objective response rates(ORR)of Crizotinib were 70.04%,73.6% and 66.9%,and the disease control rate(DCR)were 89.86%,91.5% and88.4%,respectively.The overall,first-line,and non-first-line median progression-free survival(PFS)of using Crizotinib were 12.13 months(95%CI: 9.01-15.25 months),13.37 months(95%CI: 8.05-18.69 months),and 11.8 months(95%CI: 8.52-15.08 months),respectively.Themedian overall survival(OS)of the whole group,first-line and non-first-line of using Crizotinib were 41.03 months(95%CI: 30.95-51.11 months),48 months(95%CI: 39.26-54.26 months)and39.1 months(95%CI: 31.41-46.79 months),respectively.There was no statistically significant difference between the progression-free survival and overall survival of Crizotinib among the clinical factors,such as age,gender,smoking status,etc.(P > 0.05).The personal physical status score(PS)was a factor that affected the efficiency.3.In this study,abnormal liver function was the most common adverse reaction(44.9%)in patients taking Crizotinib,Other common adverse reactions were diarrhea(27.3%),nausea and vomiting(25.6%).4.Up to the final follow-up date of March 26,2019,a total of 135 patients had disease progression,and the progression site was mostly new intracranial metastasis.5.The median PFS(ORR 62.5%,DCR 87.5%)of Alectinib was 11.2 months(95%CI:3.79-18.61 months)after Crizotinib resistance.The median PFS of Ceritinib was 10.6 months(95%CI: 0.87-20.33 months),the ORR was 86.7%,and the DCR was 100%.The median OS of Alectinib was 30.8 months(95%CI: 28.39-31.79 months).The median OS of Ceritinib was 15.6months(95%CI 14.71-16.49 months).Conclusions1.In this group,ALK-positive advanced non-small cell lung cancer patients were mostly young,non smoking history,and the pathological type was adenocarcinoma.2.Crizotinib could benefit patients with ALK-positive NSCLC patients.3.Different clinical subgroups(such as age,gender,timing of medication,transfer site,etc.)had no significant effect on the clinical efficacy(effectiveness,PFS,OS)of crizotinib.A good personal physical fitness score(PS)could bring better efficacy.4.The adverse reactions of Crizotinib were relatively mild,and the most common adverse reaction was abnormal liver function(mainly elevated transaminase).5.The Crizotinib resistance mostly occured after 12 months of taking Crizotinib,and its progression mode was mainly intracranial metastasis and single or less extracranial metastasis sites.6.Sequential use of second-and third-generation ALK-TKI after crizotinib resistance could bring significant survival benefits.