Osimertinib-Associated Cardiomyopathy In Patients With Non-Small Cell Lung Cancer

Franquiz, Miguel J.; Waliany, Sarah; Xu, Audrey Yingwei; Hnatiuk, Anna; Wu, Sean M.; Cheng, Paul; Wakelee, Heather A.; Neal, Joel; Witteles, Ronald; Zhu, Han

doi:10.1016/j.jaccao.2023.07.006

Cited by 5 publications

(4 citation statements)

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“…According to the U.S. Food and Drug Administration Adverse Events Reporting System, a pharmacovigilance database, the reporting odds ratios for cardiac failure, atrial fibrillation, and QT prolongation were significantly higher with osimertinib than with other EGFR-TKIs, such as afatinib, erlotinib, and gefitinib [ 3 ]. However, no cases of osimertinib-associated TTS have been reported until 2022 [ 4 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…TTS recurred even when a reduced dose of osimertinib was administered. A case series regarding cardiomyopathy-associated osimertinib reported that 2 of 17 patients with EGFR mutation-positive NSCLC had TTS [ 11 ]; however, other details have not yet been described. Among the patients with osimertinib-associated cardiomyopathy, approximately 60 % had at least three cardiac risk factors [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…A case series regarding cardiomyopathy-associated osimertinib reported that 2 of 17 patients with EGFR mutation-positive NSCLC had TTS [ 11 ]; however, other details have not yet been described. Among the patients with osimertinib-associated cardiomyopathy, approximately 60 % had at least three cardiac risk factors [ 11 ]. The top three most common comorbidities were hypertension (88.2 %), dyslipidemia (58.8 %), and atrial fibrillation (47.1 %).…”

Section: Discussionmentioning

confidence: 99%

“…The top three most common comorbidities were hypertension (88.2 %), dyslipidemia (58.8 %), and atrial fibrillation (47.1 %). The LVEF decreased by a median of 22 % during a median (first quartile-third quartile) of 4.2 months (3.3–9.4 months) in these patients [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Onset of takotsubo syndrome induced by osimertinib in a patient with lung adenocarcinoma

Okamoto,

Shinomiya

2024

Respiratory Medicine Case Reports

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Onset of takotsubo syndrome induced by osimertinib in a patient with lung adenocarcinoma

Okamoto,

Shinomiya

2024

Respiratory Medicine Case Reports

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Cardiac Events and Survival in Patients With EGFR-Mutant Non–Small Cell Lung Cancer Treated With Osimertinib

Lin,

Chang,

et al. 2024

JAMA Netw Open

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ImportanceAlthough it has been reported that osimertinib mesylate provides better survival benefits compared with first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), it remains unclear whether osimertinib is associated with more cancer therapy–related cardiac events (CTRCEs) compared with other EGFR TKIs, as does the extent of the association these adverse effects may have with overall survival. This issue is particularly critical due to the high prevalence of EGFR variants within Asian populations, including that of Taiwan.ObjectiveTo compare CTRCEs and their association with survival in patients treated with osimertinib vs other EGFR TKIs.Design, Setting, and ParticipantsThis cohort study was conducted at the National Cheng Kung University Hospital, a college hospital and tertiary academic referral center in Taiwan. The median follow-up duration was 23.2 (IQR, 15.2-31.5) months. A total of 401 patients with EGFR-mutant non–small cell lung cancer (NSCLC) beginning treatment with EGFR TKIs from September 1, 2019, to July 31, 2022, were retrospectively analyzed. CTRCEs included newly emerging arrhythmias, valvular heart diseases (moderate and more), myocardial infarction, and heart failure and were analyzed after adjusting for age, sex, smoking, alcohol consumption, body mass index, cardiovascular comorbidities, thoracic radiotherapy, and cardiovascular medications. Follow-up was completed January 31, 2024.ExposureOsimertinib.Main Outcomes and MeasuresThe Cox proportional hazards model was used to estimate CTRCEs in patients treated with osimertinib or other EGFR TKIs. Considering that death can lower the incidence of CTRCEs, the competing risk method was used to calculate CTRCEs after adjusting for potential confounders. Multivariable Cox proportional hazard regression analysis for overall survival was used to explore whether CTRCEs were independently associated with overall survival.ResultsAmong the 401 patients (253 [63.1%] female; mean [SD] age, 69.2 [11.3] years), 195 (48.6%) treated with osimertinib were matched with 206 (51.4%) treated with other EGFR TKIs. Occurrence of CTRCEs in patients receiving osimertinib was significantly higher compared with patients treated with other EGFR TKIs (29 [14.9%] vs 9 [4.4%]; hazard ratio [HR], 3.37; 95% CI, 1.56-7.26; P = .002). After adjustment for relevant cardiovascular risk factors, the HR of CTRCEs was significantly higher in the group treated with osimertinib (adjusted subdistribution HR, 4.00; 95% CI, 1.81-8.85; P &lt; .001). In addition, CTRCEs were independently associated with overall survival (HR, 4.02; 95% CI, 2.44-6.63; P &lt; .001).Conclusions and RelevanceIn this cohort study of patients with EGFR-mutant NSCLC, osimertinib was associated with a higher incidence of CTRCEs compared with other EGFR TKIs; CTRCEs were independently associated with overall survival. These findings highlight the need for ongoing cardiac monitoring in these patients, regardless of preexisting cardiac risk factors.

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Clinical Relevance and Mechanistic Underpinnings of Tyrosine Kinase Inhibitor Associated Cardiotoxicities

Torelli,

Agnihotri,

Zhu

et al. 2024

Curr Treat Options Cardio Med

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Purpose of Review Tyrosine kinase inhibitors (TKIs) are a major backbone of cancer treatments across a range of malignancies. Observed adverse effects of these targeted therapies include a multitude of clinically relevant cardiotoxicities distinct from those of traditional cytotoxic chemotherapies. Over the past decade, TKI cardiotoxicities have gained growing recognition in the field of cardio-oncology. Here, we aim to review clinically relevant cardiotoxicities of TKIs and incorporate relevant preclinical mechanistic data. Recent Findings Each TKI class and generation within each class have been associated with a unique cardiotoxicity profile. Broadly, documented cardiotoxicities include arrythmia (atrial and ventricular), heart failure, and vascular complications (thrombosis, endothelial dysfunction, hypertension, and atherosclerosis). Recent and progressing basic investigations have begun to unveil mechanistic underpinnings of these toxicities, such as identifying off-target perturbations of specific signaling pathways, but much more work is needed. Summary Here, we provide a review of the most clinically relevant cardiovascular toxicities to raise awareness when caring for patients on these drugs. TKIs exemplify the complexity in systemic manipulation of fundamental molecular pathways effects. Translational research in cardio-oncology is of paramount importance which can offer not only a way to better monitor (and prevent) known toxicities, but to more broadly understand and define novel molecular pathways relevant to cardiovascular disease.

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Osimertinib-Associated Cardiomyopathy In Patients With Non-Small Cell Lung Cancer

Cited by 5 publications

References 5 publications

Onset of takotsubo syndrome induced by osimertinib in a patient with lung adenocarcinoma

Onset of takotsubo syndrome induced by osimertinib in a patient with lung adenocarcinoma

Cardiac Events and Survival in Patients With EGFR-Mutant Non–Small Cell Lung Cancer Treated With Osimertinib

Clinical Relevance and Mechanistic Underpinnings of Tyrosine Kinase Inhibitor Associated Cardiotoxicities

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