Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302)

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.