Efficacy And Safety Of First Line Treatments For Patients With Advanced Non-small-cell Lung Cancer Harboring ALK Gene Rearrangement:Network Meta-analysis

Background:There are multiple first-line treatments for patients with advanced non-small cell lung cancer(NSCLC)harboring anaplastic lymphoma kinase(ALK)rearrangement.Bayesian network meta-analysis was conducted to evaluate their efficacy and safety,and rank them to provide direction for the selection of clinical protocols.Materials and Methods:Multiple databases,clinical trial registries and multiple international conference databases were searched by computer from the establishment of the database to December 13,2019 for first-line treatments of ALK-positive NSCLC patients.Published and unpublished data from randomized controlled trials are included.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR)and grade 3 or higher adverse events were clinical outcomes that have been network meta-analysed.Intracranial efficacy was subcranial analyzed additionally.Results:A total of 8 randomized controlled trials were included,with a total of 2245 patients and 5 treatments: ALK inhibitors(alectinib,brigatinib,ceritinib,crizotinib)and platinum-based chemotherapy(PbCT).The results showed that,alectinib and brigatinib were not statistically significant in prolonging PFS(HR 0.91,95% CI 0.77-1.08),but were superior to other treatments.In terms of OS,alectinib and brigatinib were not statistically significant(HR 0.85,95% CI 0.66-1.08),also with ceritinib(0.88,0.69-1.11),but were superior to brigatinib,crizotinib,and PbCT.The ORRs of ALK inhibitors were better than that of PbCT,and there were no statistical difference between ALK inhibitors.There were no statistically significant in adverse events of grade 3 or higher of various treatments.Subcranial analysis of intracranial efficacy showed that there were no statistical difference between alectinib and brigatinib in the intracranial response rate(OR 0.56,95% CI 0.04-9.20),but they were better than crizotinib(6.07,1.29-30.67;10.63,1.13-95.49,respectively).Conclusion:1.For patients with ALK-rearranged-positive advanced NSCLC,alectinib is more effective in prolonging PFS,OS and improving ORR.2.The toxic effects of various treatment methods are comparable.Alectinib has the least adverse events of grade 3 or higher.3.In patients with brain metastases,alectinib and brigatinib can better alleviate intracranial lesions.We recommend alectinib as the best option of the first-line treatment for patients with advanced ALK rearrangement-positive advanced NSCLC.However,more is needed the large-scale,multi-drug randomized controlled experiments further confirm the above results.