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

Baohui Han, Kai Li, Yizhuo Zhao, Baolan Li, Ying Cheng, Jianying Zhou, You Lu, Yuankai Shi, Zhehai Wang, Liyan Jiang, Yi Luo, Yiping Zhang, Cheng Huang, Qiang Li, Guoming Wu, Baohui Han, Kai Li, Yizhuo Zhao, Baolan Li, Ying Cheng, Jianying Zhou, You Lu, Yuankai Shi, Zhehai Wang, Liyan Jiang, Yi Luo, Yiping Zhang, Cheng Huang, Qiang Li, Guoming Wu

Abstract

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.

Conflict of interest statement

BH has consulted for AstraZeneca, Roche Pharmaceutical Company. He also received payment for speaking from AstraZeneca Pharmaceutical Company and Lily Pharmaceutical Company. All remaining authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Patient flowchart.
Figure 2
Figure 2
Comparison of progression-free survival. (A) Kaplan–Meier curves of PFS. (B) A Forest plot of PFS in the subgroups. CI=confidence interval; EGFR=epidermal growth factor receptor; HR=hazard ratio; PFS=progression-free survival.
Figure 3
Figure 3
Kaplan–Meier curves of OS. CI=confidence interval; HR=hazard ratio; OS=overall survival.

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