Analysis Of The Efficacy And Safety Of Crizotinib In The Treatment Of ALK Gene Positive ANSCLC And The Detection Of ALK

Objectives:Crizotinib, an orally small weight molecule ALK and c-MET inhibitor, is the treatment of choice for ALK+tumor patients.A series of study like profile1001/1005/1007/1014,demonstrated that crizotinib had a remarkable clinical efficacy and favorable tolerability in EML4-ALK-positive NSCLC patients. So far,only a few studies described the efficacy and tolerability of crizotinib on Chinese patient population.In the study,we will describe the clinical feature of EML4-ALK-positive NSCLC patients.and further make a summary of efficacy and tolerability of crizotinib on Chinese patient.Also,we examine feasibility of ALK rearrangement detection in targeted clinical next-generation sequencing.Method:1.We collected17ALK fusion gene positive NSCLC patients from Peking Union Medical College Hospital,who fits study criteria for medical data collection and telephone follow-up.2.We analyzed a series of3ALK rearranged lung cancers by next-generation sequencing,previously tested by fluorescence in situ hybridization (FISH).Rearrangement detection was tested using publicly available software tools, including Breakdancer and CREST.Result:1.Among17ALK fusion gene positive NSCLC patients,the age ranged from38to75years old,median age was52years old; Nine of17patients were men;only three of them had history of smoking; all of them were diagnosed with adenocarcinoma,one was diagnosed signet-ring cell carcinoma.Objective therapeutic effect：among12patients,10patients appear partial remission(PR),one patient appear stable disease(SD),and one patient appear progressive disease(PD).The total ORR is91.67%. A statistically significant (p<0.05) and clinically meaningful (≥10points) improvement from baseline was observed for patient-reported dyspnea, fatigue and global QOL.The most frequent adverse effects were anepithymia (78.87%),nausea (78.57%),Constipaton (64.29%),diarrhea (57.14%),elevated ALT (64.29) and visual effects (57.14%),mostly grade1-2.Only one patient had two SAEs:neutropenia.2.Among the3ALK FISH-positive cases,no ALK rearrangements identifications were made.The data of two samples were rejected.Conclusion:1. ALK gene fusions show a strong association with patients who have never smoked tobacco and younger age, also association with adenocarcinoma histology in China. Crizotinib demonstrated a high response rate, favorable tolerability profile and improvement in patient-reported symptoms.2.Next generation sequencing for detect ALK fusion gene is considered to have clinical prospects,but the methodology needs to be improved.And It also needs large data series to confirm feasibility of ALK rearrangement detection by NGS.