Heart Failure With Reduced Ejection Fraction Caused by Osimertinib in a Patient With Lung Cancer: A Case Report and Literature Review

Abstract

Osimertinib is widely used for the treatment of advanced lung cancers harboring epidermal growth factor receptor (EGFR) mutations. Because of its inhibitory activity on the human epidermal growth factor receptor 2 pathway, osimertinib-induced cardiotoxicity is concerning. Large-scale international clinical studies revealed a subclinical decline in the left ventricular ejection fraction (LVEF) with osimertinib, which allowed a continuation of the drug. Only a few studies have reported symptomatic heart failure with reduced ejection fraction (HFrEF) with osimertinib, and its clinical impact in real-world settings remains unclear. A 91-year-old man was diagnosed with lung adenocarcinoma harboring an EGFR L858R mutation and was started on osimertinib. The treatment conferred substantial tumor regression; however, the patient presented with symptomatic HFrEF six weeks after osimertinib initiation. Transthoracic echocardiography demonstrated diffuse hypokinesis of the left ventricular walls with a significantly reduced ejection fraction from the baseline. Initial evaluation showed no causative cause of heart failure, and we suspected osimertinib-associated cardiomyopathy. Discontinuation of the drug along with the cardioprotective approach improved cardiac symptoms and restored the LVEF to baseline within a week. Here, we comprehensively review the literature and discuss the clinical features of HFrEF following osimertinib administration. Physicians should be aware of rare complications associated with osimertinib therapy.

Delayed cardiotoxicity following osimertinib therapy in non-small cell lung cancer: a unique case report

“…Additionally, the previously reported cases of heart failure post-osimertinib administration typically manifested within a few weeks to several months, with 7 months being the longest documented duration [7,8]. However, the emergence of heart failure symptoms in this case, a notable 18 months following the initiation of osimertinib, significantly extends this observed timeline and challenges existing perceptions regarding the onset of cardiotoxicity.…”

A systematic review of epidermal growth factor receptor tyrosine kinase inhibitor-induced heart failure and its management

“…Additionally, some genetic elements play an important role in NSCLC development, including EGFR mutations, which may even explain the occurrence of NSCLC in never-smoker patients as they harbor EGFR mutations more frequently. [5] Heart failure (HF) is a clinical syndrome that develops when the heart's function is impaired and working less efficiently than normal thus it cannot keep up with the metabolic needs of the body [22]. HF has been considered a major public health issue in recent years due to its growing prevalence [23].…”

“…Anticancer treatment cardiotoxicity is typically classified into two categories; type I cardiotoxicity which is caused by anthracyclines is irreversible and is additive in a dosedependent manner. On the other hand, type II cardiotoxicity is reversible and is caused by suppression of the HER2 signaling pathway [5].…”

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer

“…A post hoc analysis of the FLAURA and AURA3 trials observed a decrease in LVEF of ≥10 percentage points to an absolute value of <50% in 3.9% of patients [41]. The data did not demonstrate a significant causal relationship, though several recent case reports have observed reversible osimertinib-induced cardiomyopathy [14,15,42]. The most frequent grade 3-4 toxicities included: neutropenia (3.4%), lymphopenia (3.3%), and hyponatremia (3.4%).…”