osimertinib and Cardiotoxicity

Oncology clinical trials demonstrate the risk of cardiotoxicity but are not sufficient to reveal the true risk. In this article, we compared the incidence of cardiotoxicity of crizotinib and osimertinib from a real-world study to data reported by phase 3 clinical trials.. Data from an ongoing real-world lung cancer study was used as a comparator. Patients were recruited retrospectively with the criteria of being diagnosed with non-small cell lung cancer and having received at least a course of treatment of tyrosine-kinase inhibitor and/or immune check-point inhibitor. Characteristics of the patients who developed cardiotoxicity associated with osimertinib and crizotinib in the real-world lung cancer study were analysed against the inclusion criteria of the corresponding phase 3 clinical trials. Variations of cardiotoxicity incidence among the real-world lung cancer study and clinical trials were investigated.. 18%, n = 37/206, of the patients developed cardiotoxicity. QTc prolongation was the most frequently observed cardiotoxicity (n = 12/37). Osimertinib and crizotinib were the most cardiotoxic agents, each responsible for seven cases of cardiotoxicity. FLAURA, AURA3, PROFILE 1007 and PROFILE 1014 were the included clinical trials for analysis. None of the patients who developed cardiotoxicity in the real-world study would have been eligible to participate in FLAURA and PROFILE 1014 study whereas n = 4/7 and n = 5/7 patients were eligible to participate in AURA3 and PROFILE 1007 trials, respectively.. Although phase 3 clinical trials play an important role in understanding the effectiveness and give insights on side-effect profiles, real-world studies can show the real risk of cardiotoxicity more accurately and realistically.

Topics: Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Crizotinib; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Retrospective Studies

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of epidermal growth factor receptor mutated non-small cell lung cancer (NSCLC). It has demonstrated better results concerning effectiveness than other TKIs for the same indication. However, despite a good safety profile, it could produce some cardiotoxicity that does not occur with other drugs of the same group.. We report the evolution and management of a female patient diagnosed with NSCLC who developed a grade 3 cardiotoxicity due to treatment with osimertinib. This patient suffered from a left bundle branch block, dyslipidemia, and hypertension as cardiovascular risk factors. After a long period of treatment with osimertinib, she developed a severe heart failure (HF) with an important decrease in left ventricular ejection fraction (LVEF), which triggered an admission to the oncology unit for eight days.. Treatment with osimertinib was first suspended and then resumed after stabilization of the HF. She also developed atrial fibrillation during admission and has required narrow cardiac monitoring and management since the debut of the HF. After evaluating the benefit-risk balance, osimertinib was reintroduced and the patient continues in treatment at the moment, although the baseline LVEF is not recovered.. There is scarce evidence in the literature concerning HF and important LVEF decrease due to osimertinib. However, its severity and repercussion for the patient justify the thorough screening of cardiovascular risk factors before starting the therapy.

Topics: Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Female; Heart Failure; Humans; Lung Neoplasms; Mutation; Stroke Volume; Ventricular Function, Left

A man in his 70s was detected an infiltrative shadow on the right lung. A bronchoscopy confirmed the diagnosis of adenocarcinoma of the lung, classified as cT2bN2M0 stage IIIA, with a deletion mutation in

Topics: Adenocarcinoma; Cardiotoxicity; ErbB Receptors; Humans; Lung; Male; Pleural Effusion

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

Topics: Acrylamides; Aniline Compounds; Cardiotoxicity; Humans

In recent years, osimertinib has been increasingly used as a therapeutic drug for epidermal growth factor receptor(EGFR)mutation-positive lung cancer, with heart failure rarely reported as an adverse event. We report here a case of a significantly decreased ejection fraction and heart failure that were induced by osimertinib. We consider the case important and include a discussion of relevant previous reports.. The patient was a 73-year-old woman who had been on oral gefitinib as first-line treatment for EGFR mutation-positive(exon19 deletion)non-small cell lung cancer for approximately 1 year and 2 months. Thereafter, she tested positive for an EGFR resistance mutation(T790M); and accordingly, oral osimerti- nib was started at 80mg/day as second-line treatment. After continuing this treatment for 6 months with no particular adverse events, she visited our hospital and was found to have dyspnea on exertion and increased pleural effusion. Based on these findings, cancer relapse was suspected, and the patient was hospitalized for detailed examinations. She was diagnosed with heart failure based on the elevated BNP level that was found in a blood test and CT and echocardiography findings, and her ejection fraction deteriorated to 19% from a pretreatment level of 59%. The conditions improved after diuretic and b- blocker treatment. Given the absence of any possible cause of heart failure or reduced ejection fraction in her past history of illness and medication, we concluded that these conditions were induced by osimertinib.. While heart failure induced by EGFR-TKIs has been rarely reported, osimertinib may cause cardiomyopathy due to human epidermal growth factor receptor type 2(HER2)inhibitory activity.

Topics: Acrylamides; Aged; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; ErbB Receptors; Female; Heart Failure; Humans; Lung Neoplasms; Mutation; Neoplasm Recurrence, Local; Protein Kinase Inhibitors; Stroke Volume