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

Kondo, Moë; Kisanuki, Megumi; Kokawa, Y.; Gohara, Seiichiro; Kawano, Osamu; Kagiyama, Shuntaro; Maruyama, Toru; Odashiro, Keita; Maehara, Yoshihiko

doi:10.3389/fcvm.2021.655808

Cited by 12 publications

(10 citation statements)

References 17 publications

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“…QTc prolongation in most cases could be a finding of low clinical significance, but in some patients, this may lead to serious consequences. The case report published by Kondo al, 17 in 2021 is very important in this regard, highlighting that this finding could be very dangerous in high-risk patients. In the reported case, an 85-year-old female on Tyrosine Kinase inhibitors had sudden death followed by QTc prolongation.…”

Section: Discussionmentioning

confidence: 93%

QTC Changes Associated with Tyrosine Kinase Inhibitors in Cancer Patients

Khattak

Ahmad

Nadeem

et al. 2022

PAFMJ

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Objective: To look for QTc changes associated with Tyrosine Kinase inhibitors and factors related to these changes among patients suffering from cancer. Study Design: Comparative cross-sectional study. Place and Duration of Study: Oncology Department, CMH Rawalpindi Pakistan from Dec 2020 to Apr 2021. Methodology: The study included one hundred and eighty patients with solid or haematological malignancies taking Tyrosine Kinase inhibitors for more than three months. They underwent 12 lead ECGs inside the oncology department. QTc interval was calculated on the ECG of all the patients, and they were evaluated for the presence of prolonged QT interval. Age, gender, duration of Tyrosine Kinase inhibitor use and presence of comorbid illness were correlated with the presence of QTc changes in our study participants. Results: Out of 180 cancer patients using Tyrosine Kinase inhibitors for more than three months included in the study, 96 (53.3%) were male, while 84 (46.7%) were female. One hundred and eighteen (65.5%) had normal QTc intervals, while 62 (34.5%) had prolonged QTc intervals in our study participants. Chi square test revealed that the advanced age of the patient and prolonged use of Tyrosine Kinase inhibitors was statistically significantly associated with QTc prolongation in our study (p-value<0.001). Conclusion: Significant number of cancer patients using Tyrosine Kinase inhibitors had prolonged QTc intervals in our study. Special attention should be paid to cancer patients with advancing age and prolonged use of Tyrosine Kinase inhibitors.

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Section: Discussionmentioning

confidence: 93%

QTC Changes Associated with Tyrosine Kinase Inhibitors in Cancer Patients

Khattak

Ahmad

Nadeem

et al. 2022

PAFMJ

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“…Furthermore, osimertinib-induced QT prolongation leading to the possible development of Torsades de Pointes (TdP) is still unclear. 10 Osimertinib safety was first assessed in 253 patients treated in the escalation and expansion cohorts from the AURA 1 study. QTc prolongation was reported in 11 patients, but they did not require dose reduction or drug discontinuation.…”

Section: Discussionmentioning

confidence: 99%

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

Bardaro

Stirpe

2022

J Oncol Pharm Pract

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Introduction 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. Case report 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. Management and outcome 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. Discussion 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.

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“…No Tdp associated with osimertinib has occurred in clinical trials ( 4 , 5 ), and only three cases of Tdp caused by osimertinib have been reported ( Table 2 ). In addition, Kondo ( 25 ) reported a case of an 85-year-old female patient treated with osimertinib for advanced lung cancer expressing EGFR mutations (T790M), which lengthened QT interval causing abortive sudden cardiac death (SCD). Cardiac arrest in that case was supposed to be due to possible development of TdP based on several predisposing factors lengthening QT interval.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Torsade de Pointes Induced by the Third-Generation Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor Osimertinib Combined With Litsea Cubeba

Zhang

et al. 2022

Front. Cardiovasc. Med.

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Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named “Litsea Cubeba” may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated. However, QT prolongation sustained at discharge (QTc = 528 ms), partly because of the emergency use of amiodarone. Osimertinib may prolong the QT interval leading to TdP, especially when multiple risk factors to lengthen QT interval are incidentally overlapped. Thus, regular monitoring of ECG and appropriate management of concomitant drugs are highly recommended.

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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

Cited by 12 publications

References 17 publications

QTC Changes Associated with Tyrosine Kinase Inhibitors in Cancer Patients

QTC Changes Associated with Tyrosine Kinase Inhibitors in Cancer Patients

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

Case Report: Torsade de Pointes Induced by the Third-Generation Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor Osimertinib Combined With Litsea Cubeba

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