BACKGROUND: Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, 
inhibiting tumour angiogenesis and proliferative signalling. The objective of 
this study was to assess the safety and efficacy of third-line anlotinib for 
patients with refractory advanced non-small-cell lung cancer (RA-NSCLC).
METHODS: Eligible patients were randomised 1 : 1 to receive anlotinib (12 mg per 
day, per os; days 1-14; 21 days per cycle) or a placebo. The primary end point 
was progression-free survival (PFS).
RESULTS: A total of 117 eligible patients enrolled from 13 clinical centres in 
China were analysed in the full analysis set. No patients received immune 
check-point inhibitors and epidermal growth factor receptor status was unknown 
in 60.7% of the population. PFS was better with anlotinib compared with the 
placebo (4.8 vs 1.2 months; hazard ratio (HR)=0.32; 95% confidence interval 
(CI), 0.20-0.51; P<0.0001), as well as overall response rate (ORR) (10.0%; 95% 
CI, 2.4-17.6% vs 0%; 95% CI, 0-6.27%; P=0.028). The median overall survival (OS) 
was 9.3 months (95% CI, 6.8-15.1) for the anlotinib group and 6.3 months (95% 
CI, 4.3-10.5) for the placebo group (HR=0.78; 95% CI, 0.51-1.18; P=0.2316). 
Adverse events were more frequent in the anlotinib than the placebo group. The 
percentage of grade 3-4 treatment-related adverse events was 21.67% in the 
anlotinib group.
CONCLUSIONS: Anlotinib as a third-line treatment provided significant PFS 
benefits to patients with RA-NSCLC when compared with the placebo, and the 
toxicity profiles showed good tolerance.