• Zhonghan Zhang, Yuanyuan Zhao, Feiteng Lu, Xue Hou, Yuxiang Ma, Fan Luo, Kangmei Zeng, Shen Zhao, Yaxiong Zhang, Ting Zhou, Yunpeng Yang, Wenfeng Fang, Yan Huang, Li Zhang, and Hongyun Zhao.
• Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
• Ann Transl Med. 2019 Sep 1; 7 (18): 452.

BackgroundFour multi-targeted tyrosine kinase inhibitors (TKIs) including apatinib, anlotinib, fruquintinib and lenvatinib are currently available as third-line regimen for advanced non-small cell lung cancer (NSCLC) patients who failed at least two lines of systemic therapy. Limited evidence was provided to demonstrate the general efficacy and safety profile of these drugs as third-line treatment approach for NSCLC.MethodsEligible literature was searched from electronic database. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment related adverse event (TRAE), treatment related adverse event grade 3-5 (TRAE3-5), hypertension, proteinuria, hand-foot skin reaction (HFSR), elevated ALT/AST, nausea and vomiting, diarrhea were synthetically extracted. Multiple-treatments comparisons (MTCs) based on a Bayesian consistency model integrated the efficacy and toxicity outcomes. Rank probabilities of each regimen were assessed and clustered by the surface under the cumulative ranking curve.ResultsFive phase II/III randomized trials involving 915 advanced NSCLC patients were enrolled. MTCs showed that four multi-targeted TKIs shared equivalent efficacy in terms of outcome measures, of which anlotinib stood out in ORR (OR =39.26; 95% CI: 2.36-2,748.06), DCR (OR =8.69; 95% CI: 1.70-50.18) and PFS (HR =0.27; 95% CI: 0.10-0.78) when compared with placebo plus BSC. No significantly differences were observed among these TKIs and placebo with respect to OS, TRAE and TRAE 3-5. Fruquintinib and lenvatinib may relate to high rate of HFSR while anlotinib may relate to hypertension.ConclusionsMulti-targeted TKIs (apatinib, anlotinib, fruquintinib and lenvatinib) with acceptable efficacy and safety profile were options for advanced NSCLC in third-line setting.2019 Annals of Translational Medicine. All rights reserved.

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