Management of anlotinib-related adverse events in patients with advanced non-small cell lung cancer: Experiences in ALTER-0303

Xiaoyan Si, Li Zhang, Hanping Wang, Xiaotong Zhang, Mengzhao Wang, Baohui Han, Kai Li, Qiming Wang, Jianhua Shi, Zhehai Wang, Ying Cheng, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin, Xiaoyan Si, Li Zhang, Hanping Wang, Xiaotong Zhang, Mengzhao Wang, Baohui Han, Kai Li, Qiming Wang, Jianhua Shi, Zhehai Wang, Ying Cheng, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin

Abstract

Background: Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, and stem cell factor receptor (c-Kit). In the phase III ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial.

Methods: Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and managed by investigators. Key strategies for preventing and managing the most common adverse events included patient education, supportive care, and dose modification.

Results: Between February 2015 and August 2016, 294 patients received anlotinib. A total of 170 (57.8%) patients received antihypertensive medications for hypertension, 53 (18.0%) patients received levothyroxine for hypothyroidism, 24 (8.2%) patients received fibrates for hypertriglyceridemia, 11 (3.7%) patients took cortisone cream for hand-foot syndrome, and 38 (12.9%) patients received anti-diarrheal medications for diarrhea. Dose reduction and drug discontinuation were required in 24 (8.16%) and 31 (10.54%) patients in the anlotinib group, respectively.

Conclusion: Anlotinb-related adverse events could be controlled by patient education, prophylactic measures, early and active intervention, and dose modification.

Keywords: Adverse event; anlotinib; multi-target tyrosine kinase inhibitor; non-small cell lung cancer.

© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

References

    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893–917.
    1. Sun Y, Niu W, Du F et al Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi‐target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol 2016; 9: 105.
    1. Han B, Li K, Zhao Y et al Anlotinib as a third‐line therapy in patients with refractory advanced non‐small‐cell lung cancer: A multicentre, randomised phase II trial (ALTER0302). Br J Cancer 2018; 118: 654–61.
    1. Afonso FJ, Anido U, Fernandez‐Calvo O et al Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor. Clin Transl Oncol 2013; 15: 425–33.
    1. Porta C, Gore ME, Rini BI et al Long‐term safety of Sunitinib in metastatic renal cell carcinoma. Eur Urol 2016; 69: 345–51.
    1. Han B, Li K, Wang Q et al Effect of anlotinib as a third‐line or further treatment on overall survival of patients with advanced non‐small cell lung cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol 2018; 4: 1569–75.
    1. Si X, Zhang L, Wang H et al Quality of life results from a randomized, double‐blinded, placebo‐controlled, multi‐center phase III trial of anlotinib in patients with advanced non‐small cell lung cancer. Lung Cancer 2018; 122: 32–7.
    1. Han B, Li K, Zhao Y et al P2.03a‐001 A randomized phase III clinical trial of anlotinib hydrochloride in patients with advanced non‐small cell lung cancer (NSCLC). J Thorac Oncol 2017; 12: S886–7.
    1. Cheng AL, Kang YK, Chen Z et al Efficacy and safety of sorafenib in patients in the Asia‐Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double‐blind, placebo‐controlled trial. Lancet Oncol 2009; 10: 25–34.
    1. Lee SH, Bang YJ, Mainwaring P et al Sunitinib in metastatic renal cell carcinoma: An ethnic Asian subpopulation analysis for safety and efficacy. Asia Pac J Clin Oncol 2014; 10: 237–45.
    1. Maitland ML, Bakris GL, Black HR et al Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst 2010; 102: 596–604.
    1. Abdel‐Rahman O, Fouad M. Risk of thyroid dysfunction in patients with solid tumors treated with VEGF receptor tyrosine kinase inhibitors: A critical literature review and meta analysis. Expert Rev Anticancer Ther 2014; 14: 1063–73.
    1. Zhou A. Management of sunitinib adverse events in renal cell carcinoma patients: The Asian experience. Asia Pac J Clin Oncol 2012; 8: 132–44.
    1. Schmidinger M. Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors. EJC Suppl 2013; 11: 172–91.
    1. Shi J, Han B, Li K et al Subgroup analysis of elderly patients (pts) in ALTER0303: Anlotinib hydrochloride as 3rd‐line and further line treatment in refractory advanced NSCLC pts from a randomized, double‐blind, placebo‐controlled phase III ALTER0303 trial. J Clin Oncol 2018; 36: e21181.
    1. Li K, Wang J, Han B et al P3.01‐087 impact factor analysis for efficacy and prognosis of Anlotinib in NSCLC as third‐line treatment: Data from trial ALTER 0303. J Thorac Oncol 2017; 12: S2236.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera