A case of torsades de pointes induced by the third-generation EGFR-TKI, osimertinib combined with moxifloxacin

Abstract

Background: Torsade de pointes (TdP) is a malignant arrhythmia that can be induced by QT internal prolongation due to a variety of factors. Here we report an elderly patient with advanced non-small cell lung cancer (NSCLC) had sudden TdP during hospitalization, which was caused by multiple factors such as osimertinib, moxifloxacin and patient self-factors. Case presentation: An 85-year-old man with advanced NSCLC with brain andbone metastasis was initially treated with gefitinib targeted therapy. After 4 months treatment, the patient developed drug resistance and a second genetic testing revealed that the T790M mutation was positive. And the patient was then changed to targeted therapy with osimertinib, followed by adverse reactions of varying severity such as diarrhea, electrolyte imbalance, decreased cardiac function, leukopenia, and prolonged QTc interval. Six months after the administration of osimertinib, the patient was admitted to the hospital, chest CT showed the lesion progressed again, and during which hospital-acquired infection occurred. After concomitant use of moxifloxacin, the patient had sudden TdP, and finally died of this cardiac event. Conclusions: It is suggested that clinicians need to identify patients with high risk factors of TdP, and consider comprehensively in concomitant medication to avoid such events to the greatest extent.

Osimertinib induced cardiac failure and QT-prolongation in a patient with advanced pulmonary adenocarcinoma

“…Although it is useful to reduce disagreement between speakers and to categorize the probability of ADRs, after all, these algorithms neither confirm causality nor do they accurately measure the likelihood of an ADR 3,6 To our knowledge, only three cases of coincidence cardiac dysfunction and QT prolongation caused by Osimertinib have been reported. [7][8][9] The etiology of Osimertinib-induced cardiotoxicity is unclear. It has been suggested that Osimertinib has a similar effect to that Trastuzumab, a monoclonal antibody against human EGFR2.…”

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

“…QT interval is lengthened as a result of ventricular potassium current reduction and late sodium current augmentation ( 4 ). Bian et al ( 5 ) reported a first case of 85-year-old male patient with advanced non-small cell lung cancer associated with TdP induced by oral osimertinib (80 mg once daily) and concomitant intravenous moxifloxacin, a broad-spectrum fluoroquinolone antibiotics known to lengthen the QT interval (QTc of 484 ms). Hypokalemia (2.94 mEq/L), impaired left ventricular ejection fraction (41%) and coadministration of moxifloxacin were concluded to underlie the development of TdP.…”

“…Hypokalemia (2.94 mEq/L), impaired left ventricular ejection fraction (41%) and coadministration of moxifloxacin were concluded to underlie the development of TdP. They lost this case and hence cautioned cardio-oncologists to identify cancer patients at high risk of QT prolongation leading to the development of TdP ( 5 ). Cancer development and apoptosis is governed by driver mutation of signal transduction process mediated by several growth factor receptor including EGFR which is linked to many potassium channels, i.e., Kv1.3 ( 6 ), Kv10.1 ( 7 ), Kv4.3 ( 8 ), and Kir2.3 ( 9 ) are modulated by EGFR kinase via phosphorylation of tyrosine in their specific residues.…”

Alkalescent soda beverage caused the disappearance of gefitinib-induced rashes and decreased efficacy in a non-small-cell lung cancer patient treated with gefitinib: A case report

“…However, from the above discussion, it should be noted that gefitinib is not suitable for taking with alkaline food that elevate gastric pH. In addition, during EGFR-TKIs treatment, concomitant medication should also be considered comprehensively to achieve optimal therapeutic outcome [ 14 ].…”