Anlotinib for refractory advanced non-small-cell lung cancer: A systematic review and meta-analysis

Abstract

Objective: To assess the efficacy and toxicity of anlotinib for the treatment of refractory advanced non-small-cell lung cancer (NSCLC).

Methods: We systematically searched databases for randomized controlled trials on anlotinib treatment for patients with advanced NSCLC published until November 6, 2020. Articles were assessed and data were extracted independently by two investigators. Further, we analyzed hazard ratios (HRs) for progression-free and overall survival (PFS and OS, respectively). In addition, we analyzed risk ratio (RR) for overall response and disease control rates (ORR and DCR, respectively) and the odds ratio (OR) for the main adverse events (AEs) using RevMan 5.3 software.

Results: This analysis included 594 patients from three clinical studies. The pooled HRs for PFS and OS were 0.27 (95% confidence interval (CI): 0.22-0.33, P < 0.001) and 0.68 (95% CI: 0.56-0.83, P < 0.001), respectively, indicating that anlotinib administration significantly improved PFS and OS in patients with advanced NSCLC. The pooled RRs for ORR and DCR were 11.62 (95% CI: 2.75-49.14, P < 0.001) and 2.30 (95% CI: 1.91-2.77, P < 0.001), respectively, indicating that anlotinib administration in patients with advanced NSCLC improved ORR and DCR. The pooled OR for AEs of grade 3 or higher was 2.94 (95% CI: 1.99-4.35, P < 0.001), indicating that AEs of grade 3 or higher were more prevalent in the anlotinib group than in the placebo group.

Conclusion: Anlotinib, an effective choice of third- or later line therapy for patients with refractory advanced NSCLC, provides clinical benefits in terms of PFS, OS, ORR, and DCR. AEs associated with anlotinib were tolerable.

Fig 1. Diagram of the literature search and trial selection process in the meta-analysis.

57, 128, 49, 97, and 97 articles were found in PubMed, the Cochrane Library, Embase, CNKI, and Wanfang database, respectively.

Fig 2. Diagram of the risk of bias in the included studies.

Fig 3. Forest plot comparing the PFS between anlotinib and placebo group in advanced NSCLC.

The red squares represent the HR of a study, and the black line their confidence intervals. The black diamond represent the pooled HR and its confidence interval.

Fig 4. Forest plot comparing the OS between the anlotinib and placebo groups with advanced NSCLC.

The red squares represent the HR of a study, and the black line their confidence intervals. The black diamond represent the pooled HR and its confidence interval.

Fig 5. Forest plot comparing the ORR between anlotinib and placebo group in advanced NSCLC.

The blue squares represent the RR of a study, and the black line their confidence intervals. The black diamond represent the pooled RR and its confidence interval.

Fig 6. Forest plot comparing the DCR between the anlotinib and placebo groups with advanced NSCLC.

The blue squares represent the RR of a study, and the black line their confidence intervals. The black diamond represent the pooled RR and its confidence interval.