Current perspective: Osimertinib-induced QT prolongation: new drugs with new side-effects need careful patient monitoring

Eur J Cancer. 2018 Mar:91:92-98. doi: 10.1016/j.ejca.2017.12.011.


An increasing number of tyrosine kinase inhibitors (TKIs) are available for the treatment of non-small cell lung cancer (NSCLC). QT prolongation is one of the known, but relatively rare, adverse events of several TKIs (e.g. osimertinib, crizotinib, ceritinib). Screening for QT prolongation in (high risk) patients is advised for these TKIs. When a QT prolongation develops, the physician is challenged with the question whether to (permanently) discontinue the TKI. In this perspective, we report on a patient who developed a grade III QT prolongation during osimertinib (a third-generation epidermal growth factor receptor [EGFR]-TKI) treatment. On discontinuation of osimertinib, she developed a symptomatic disease flare, not responding to subsequent systemic treatment. The main aim of this perspective is to describe the management of QT prolongation in stage IV EGFR driver mutation NSCLC patients. We also discuss the ethical question of how to weigh the risk of a disease flare due to therapy cessation against the risk of sudden cardiac death. A family history of sudden death and a prolonged QT interval might indicate a familiar long QT syndrome. We have summarised the current monitoring advice for TKIs used in the treatment of lung cancer and the most common drug-TKI interactions to consider and to optimise TKI treatment in lung cancer patients.

Keywords: Disease flare; Drug monitoring; Non-small cell lung cancer; QT interval; Tyrosine kinase inhibitor.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acrylamides
  • Adenocarcinoma / diagnostic imaging
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Aniline Compounds
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Decision-Making
  • Drug Monitoring*
  • Electrocardiography
  • ErbB Receptors / genetics
  • Fatal Outcome
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / physiopathology
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Phenotype
  • Piperazines / adverse effects*
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / adverse effects*
  • Risk Assessment
  • Risk Factors
  • Tomography, X-Ray Computed


  • Acrylamides
  • Aniline Compounds
  • Antineoplastic Agents
  • Piperazines
  • Protein Kinase Inhibitors
  • osimertinib
  • EGFR protein, human
  • ErbB Receptors