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

Thorac Cancer. 2019 Mar;10(3):551-556. doi: 10.1111/1759-7714.12977. Epub 2019 Jan 21.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug-Related Side Effects and Adverse Reactions / classification
  • Drug-Related Side Effects and Adverse Reactions / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Female
  • Hand-Foot Syndrome / drug therapy
  • Hand-Foot Syndrome / etiology
  • Hand-Foot Syndrome / pathology
  • Humans
  • Hypertension / chemically induced
  • Hypertension / drug therapy
  • Hypertension / pathology
  • Hypertriglyceridemia / chemically induced
  • Hypertriglyceridemia / drug therapy
  • Hypertriglyceridemia / pathology
  • Hypothyroidism / chemically induced
  • Hypothyroidism / drug therapy
  • Hypothyroidism / pathology
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Thyroxine / administration & dosage

Substances

  • Indoles
  • Protein Kinase Inhibitors
  • Quinolines
  • anlotinib
  • Anaplastic Lymphoma Kinase
  • ErbB Receptors
  • Thyroxine