osimertinib and Long-QT-Syndrome

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.

Topics: Acrylamides; Adenocarcinoma; Adenocarcinoma of Lung; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Clinical Decision-Making; Drug Monitoring; Electrocardiography; ErbB Receptors; Fatal Outcome; Female; Genetic Predisposition to Disease; Humans; Long QT Syndrome; Lung Neoplasms; Middle Aged; Mutation; Neoplasm Staging; Phenotype; Piperazines; Predictive Value of Tests; Protein Kinase Inhibitors; Risk Assessment; Risk Factors; Tomography, X-Ray Computed

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) used for the treatment of non-small cell lung cancer (NSCLC) presenting an EGFR mutation. Although Osimertinib has a better safety profile compared to older EGFR-TKIs and although adverse events (AEs) are described in literature, recently the relationship between Osimertinib therapy and cardiotoxicity is gaining attention.. A 79-years old woman, with a history of lung adenocarcinoma on treatment with Osimertinib since 2019, was recovered in our department because of acute respiratory failure and acute heart failure with QT prolongation. The patient's history included hypertension, type 2 diabetes, breast carcinoma, Tuberculosis.. The patient discontinued Osimertinib therapy and we treated her with diuretics, ß-blocker, and oxygen. After an initial improvement, the heart failure worsened further, and the therapy had to be increased. We ruled out other respiratory causes of heart failure and cardiological causes of QT prolongation. After stable clinical improvement, the patient underwent coronary artery disease which was negative. Therefore, the most likely cause of acute heart disease was Osimertinib therapy.. This is a rare case of concomitant QT prolongation and congestive heart failure induced by Osimertinib therapy. The cause of cardiotoxicity probably depends on factors related to the action of the drug and patient specific factors. The cardiotoxic risk in these patients seems underestimated and cardiotoxicity induced by new anticancer treatments is increasing in importance. Cardiac monitoring is recommended in neoplastic patients receiving Osimertinib therapy with cardiological risk factors.

Topics: Acrylamides; Adenocarcinoma; Adenocarcinoma of Lung; Aged; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Diabetes Mellitus, Type 2; ErbB Receptors; Female; Heart Failure; Humans; Long QT Syndrome; Lung Neoplasms; Mutation; Protein Kinase Inhibitors