Real-world Study Of Crizotinib In The Treatment Of Advanced ALK/ROS-1-positive Non-small Cell Lung Cancer

Purpose: Targeted therapy is a major breakthrough in the treatment of NSCLC.The excellent performance of gefitinib marked the beginning of the targeted therapy.Except the EGFR-positive patients,ALK-positive patients are important part of NSCLC patients.In 2011,the US FDA approved the first-line treatment of crizotinib in ALK-positive metastatic or locally advanced non-small cell lung cancer,based on the PROFILE1014 study.In 2013,the CFDA approved crizotinib as first-line treatment for ALK-positive metastatic or locally advanced non-small cell lung cancer.In June 2012,crizotinib was launched in China.In order to make clear the real-world situation of crizotinib,we began to collect clinical and pathological data from patients treated with crizotinib and followed up clinically to observe the efficacy and adverse effects.The main objectives of our study are as follows: 1.Describe the clinical and pathological features of patients treated with crizotinib.2.Observe the efficacy of crizotinib in the real world.3.To explore the efficacy of crizotinib and its relationship with clinicopathological features.4.Observe the adverse effects of crizotinib in the real world.Materials and Methods: From October 2012 to May 2018,64 patients were enrolled,and 64 patients were ALK/ROS-1 positive NSCLC patients who were treated with crizotinib for advanced or locally advanced or postoperative relapse.Most of them are outpatients or hospitalized patients in our hospital.All patients received imaging examination within 1 month before the treatment as baseline,and the first imaging examination was performed 1 month after crizotinib treatment.The evaluation was performed with RECIST 1.1 solid tumor evaluation criteria.There is an imaging examination every 2 months thereafter.Hematology examinations are performed monthly.Result: 1.Clinical and pathological features of patients 1.1 Clinical features A total of 64 patients were included in the study.Men accounted for 37.5%(24/64),women accounted for 62.5%(40/64),aged between 26 and 75,average age is 51.34.1.2 Pathological features Among the 64 patients,89.1%(57/64)were adenocarcinoma,4.7%(3/64)were adenosquamous carcinoma,3.1%(2/64)were squamous cell carcinoma,and 1.6%(1/64)were sarcomatoid cancer.Pathology unknow was 1.6%(1/64).2.The efficacy of crizotinib One month after the patient took the drug,we began to evaluate the efficacy.The results were as follows: The objective response rate was 67.2% and the disease control rate was 98.4%.We used the Kaplan-Meier method to map the survival curves of the entire group,including PFS and OS.The results were as follows: m PFS(median progression-free survival)was 17.0 months(95% CI 13.1 months to 20.8 months),and m OS(median over-all survival)was 32.0 months(95% CI 27.2 months-36.7 month).3.Relationship between efficacy evaluation and clinicopathological features 3.1 Summary of single factor analysis results: 1)The age of the patient(?60 years old and <60 years old)is related to OS and ORR.2)There is a correlation between the patient's pathological type(adenocarcinoma and non-adenocarcinoma)and PFS.3)Platelet counts(>300 and ?300)are related to OS.4)Factors unrelated to ORR: gender,smoking history,stage of disease,treatment opportunity with crizotinib,baseline brain metastasis,No.of metastatic organs,pathology site,test method,pathological type,platelet count.Factors unrelated to PFS: age,gender,smoking history,stage of disease,treatment oppotunity with crizotinib,baseline brain metastases,number of metastatic organs,pathology site,test method,platelet count,BMI,NLR.Factors unrelated to OS: gender,smoking history,stage of disease,treatment opportunity with crizotinib,baseline brain metastasis,No.of metastatic organs,pathology site,test method,BMI,NLR.3.2 Multivariate analysis results summary: Age and platelet count were statistically correlated with OS.Treatment opportunity,pathological type were statistically correlated with OS.There was no statistically significant association between age,treatment opportunity,pathological type,platelet count,and PFS.4.AE The common adverse event in patients were elevated transaminases,hypoproteinemia,nausea and vomiting,visual abnormalities,decreased neutrophil count,diarrhea,and limb edema.Most AE level are 1-2.Conclusion: 1.The clinical character of this group of patients: younger,female,non-smoking,adenocarcinoma.2.ALK/ROS-1 positive patients with advanced NSCLC,disease control rate,objective response rate,median progression-free survival,median overall survival were 98.4%,67.2%,17 months,32 months.3.Older age or high platelet counts patients with oral crizotinib in ALK/ROS-1 positive NSCLC have a poor prognosis.4.Crizotinib is likely to be effective for ALK-positive specific pathological types and ROS-1 positive lung cancer patients.5.Crizotinib adverse reactions is tolerated,grade 3/4 adverse event are elevated transaminase,and neutropenia.