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

Abstract

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.

Retrospective Analysis of Skin Toxicity in Patients under Anti-EGFR Tyrosine Kinase Inhibitors: Our Experience in Lung Cancer

“…As already reported by Derrick Chen-Wee Aw et al, our study confirms that afatinib causes rash more frequently than erlotinib, gefitinib and osimertinib [8], [11]. We only had two patients under osimertinib therapy, and one of them developed a rash (50% of total patients), but we cannot conclude that osimertinib causes rash as frequently as first or second generation TKIs since our data were conducted on a few numbers of patients.…”

Case Report: QT Prolongation and Abortive Sudden Death Observed in an 85-Year-Old Female Patient With Advanced Lung Cancer Treated With Tyrosine Kinase Inhibitor Osimertinib

“…Osimertinib is an oral, third-generation TKI as an emerging therapeutic modality in various cancers with EGFR T790M mutation (2). One of the obstacles for wide use of this promising anticancer agent is QT prolongation.…”

“…Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is a first-line therapy for patients with cancer expressing epidermal growth factor receptor (EGFR) mutations. This anticancer drug has adverse effects including cardiotoxicity such as coronary tonus elevation and QT prolongation in electrocardiogram (ECG), because vascular and cardiac potassium channels are regulated largely by EGFR tyrosine kinase (2). However, osimertinib-induced QT prolongation leading to the possible development of Torsades de Pointes (TdP) has received less attention (3).…”

The Use of Traditional Chinese Medicine in Relieving EGFR-TKI-Associated Diarrhea Based on Network Pharmacology and Data Mining

“…Dysfunction of this target will cause excess sodium to enter the cardiomyocytes through abnormal channels, which leads to long QT syndrome [ 45 ]. Related studies have shown that QT interval prolongation is a relatively rare adverse event of several TKIs such as osimertinib and crizotinib, and it is believed that the heart should be monitored during the treatment of axitinib in patients with a previous family history of heart disease [ 46 ].…”