Efficacy and Safety of Anlotinib in Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Study

Background: Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) independently developed by China, which can inhibit tumor angiogenesis and tumor cell proliferation. The ALTER 0303 study has suggested that anlotinib improved overall survival (OS) and progression-free survival (PFS) in the treatment of advanced non-small cell lung cancer (NSCLC). However, in the real world, the efficacy and safety of anlotinib is not clear. Although relevant retrospective studies have confirmed the efficacy and safety of anlotinib, the sample size is small. And the OS was not observed because of the follow-up time was short. Further studies are still essential to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC in real-world settings. Related studies have preliminarily shown that anlotinib combined with whole-brain radiotherapy (WBRT) can significantly prolong the survival of patients with brain metastases of NSCLC. This study also discusses the best treatment strategies of patients with brain metastases. Methods: A retrospective study was conducted on 206 patients with advanced NSCLC who had treated with anlotinib. The primary endpoints were PFS and OS. The secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Kaplan-Meier survival curves were applied to evaluate the efficacy. Univariate analysis was performed by Log rank testing. Cox regression analysis was utilized to evaluate the significance of potential risk factors obtained from the univariate analysis. Results: The median PFS (mPFS) was 4.0 (95% CI: 3.607-4.393) months, univariate analysis revealed that patients with longer PFS included epidermal growth factor receptor (EGFR) mutation-negative, Eastern Cooperative Oncology Group performance status (ECOG PS) <= 1, no brain metastases, no liver metastases, no adrenal metastases, or <= 2 distant metastases. Cox regression analysis indicated that patients with EGFR-negative and ECOG PS <= 1 had longer PFS. The median OS (mOS) was 8(95% CI: 6.495-9.505) months. EGFR mutation-negative, previous thoracic radiation therapy, no brain metastases, or <= 2 distant metastases were independent positive predictors of OS. The results of Cox regression indicated that the patients without previous thoracic radiation therapy (hazard ratio: 1.855; 95% CI: 1.162-2.960; p=0.010) had shortened OS. The objective response rate was 10.2%, and the disease control rate was 78.2%. The main treatment-related adverse events (AEs) were generally tolerated. All AEs observed during the trial were controlled after dose reduction or symptomatic treatments, and no death was found to be associated with anlotinib. Conclusion: Anlotinib was well tolerated and effective in patients with advanced NSCLC. Patients with EGFR mutation-negative and ECOG PS <= 1 had longer PFS, and patients without previous thoracic radiation therapy (HR: 1.855, 95% CI 1.162-2.960; P = 0.010) had shorter OS. Further investigations are needed because of small sample.