Incidence of cardiac toxicities in patients with advanced non-small cell lung cancer treated with osimertinib: A combined analysis of two phase III randomized controlled trials

Thein, Kyaw Zin; Swarup, Sriman; Ball, Somedeb; Quirch, Miguel; Vorakunthada, Yuttiwat; Htwe, Khaing Khaing; D’Cunha, Nicholas; Hardwicke, Fred; Awasthi, Sanjay; Tijani, Lukman

doi:10.1093/annonc/mdy292.011

Cited by 13 publications

(7 citation statements)

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“…Recent data have shown that osimertinib is associated with an increased risk of QTc prolongation, AF, VTE, LVD, and HF (Figure 22). 373,374 A study of 123 patients with EGFR-mutant non-small cell lung cancer treated with osimertinib reported a 4.9% incidence of HF or MI and a significant decrease in LVEF ,53% in 11% of patients with TTE surveillance. 375 Pre-existing hypertension and older age are risk factors for LVD and HF (3.9% and 2.6% incidence, respectively).…”

Section: Epidermal Growth Factor Receptor Inhibitorsmentioning

confidence: 99%

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

Lyon¹,

López‐Fernández²,

Couch³

et al. 2022

European Heart Journal

1,242

934

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Coronary care unit CDK Cyclin-dependent kinase CHA 2 DS 2 -VASc Congestive heart failure, Hypertension, Age ≥ 75 years (2 points), Diabetes mellitus, Stroke (2 points)-Vascular disease, Age 65-74 years, Sex category (female) CIED Cardiac implantable electronic device CML Chronic myeloid leukaemia CMR Cardiac magnetic resonance COMPASS-CAT Prospective COmparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real-life patients-Cancer Associated Thrombosis CPET Cardiopulmonary exercise testing CrCl Creatinine clearance CRF Cardiorespiratory fitness CRS Cytokine release syndrome CS Cancer survivors CT Computed tomography CTLA-4 Cytotoxic T lymphocyte-associated antigen-4 cTn Cardiac troponin CTRCD Cancer therapy-related cardiac dysfunction CTR-CVT Cancer therapy-related cardiovascular toxicity CV Cardiovascular CVD Cardiovascular disease CVRF Cardiovascular risk factorsData derived from a single randomized clinical trial or large non-randomized studies.Consensus of opinion of the experts and/or small studies, retrospective studies, registries.©ESC 2022 ESC Guidelines © ESC 2022This table refers to anthracycline equivalence dose using doxorubicin as a reference. Note that these isoequivalent doses are derived from paediatric CS. CS, cancer survivors; CV, cardiovascular.a Data for idarubicin are based upon an estimated anticancer efficacy ratio, not derived from cardiotoxicity data. The CV toxicity dose ratio provides the value that should be used to multiply the dose of the anthracycline of interest to convert to isoequivalent doses of doxorubicin; e.g. to convert 125 mg/m 2 of epirubicin to doxorubicin isoequivalent, multiply the dose by 0.8 (125 mg/m 2 × 0.8 = 100 mg/m 2 of doxorubicin).

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Section: Epidermal Growth Factor Receptor Inhibitorsmentioning

confidence: 99%

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

Lyon¹,

López‐Fernández²,

Couch³

et al. 2022

European Heart Journal

1,242

934

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“…In another Japanese report, 2.5% of the patients suffered from heart failure during osimertinib course [38]. A meta-analysis showed that osimertinib had a significant association with QT prolongation and increased hazard for heart failure as well [39].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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Background Multiple case reports and case series have been published on heart failure due to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), yet the management and outcome of the said disease have been scarcely discussed in sufficient details. This review is aimed at characterizing the signs, symptoms, laboratory parameters, and outcomes of this entity by analyzing recent published case reports and case series reporting new-onset heart failure in non-small cell lung cancer tumor (NSCLC) patients who are being treated with EGFR TKIs. Methods This is a systematic review of case reports and case series for cases of EGFR TKI-induced heart failure. A systematic search was conducted across a number of databases starting with PubMed databases utilizing its MeSH database; after that, a complementary search through Google Scholar was conducted. Results In total, 23 cases of epidermal growth factor receptor tyrosine kinase inhibitor-induced heart failure were included. The majority of the reported case were females (20 females and three males) with a male-to-female ratio of 1:6.6. Ages ranged from 47 to 91 years of age with a mean age of 70.73 and a median of 71 years of age. Symptom improvement and being symptom-free from a heart failure perspective after treatment from the acute event were observed in 18 cases (78.26%) while heart failure progressively worsened and led to the death of the patient in only one case (4.3%). Conclusion The utilization of EGFR TKIs in NSCLCs has been associated with a better outcome and fewer side effects when compared to classical chemotherapeutic agents. However, cardiotoxic effects, such as heart failure, could be significant for a small proportion of patients. Recent papers have reported heart failure in younger and cardiac risk-free patients. Still, it is only advised to monitor for heart failure in the high-risk group. Treatment should be individualized and based on a case-by-case basis.

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“…Despite their low incidence, cardiotoxicities including congestive heart failure, QT prolongation, and vital arrhythmias have become a safety concern for patients taking EGFR TKIs. Osimertinib-induced QT prolongation was first reported during the phase I trials for the drug ( 7 ), after which analyses in two phase III randomized controlled trials also confirmed that osimertinib notably increased the risk of cardiac toxicities, with a risk ratio of 2.62 for QT prolongation ( 8 ). The initial FDA risk-benefit assessment reported a low incidence (0.7%) of osimertinib-induced substantial QTc prolongation (QTc ≥ 500 msec), with no QTc-related VAs reported ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Overdrive pacing in the acute management of osimertinib-induced ventricular arrhythmias: A case report and literature review

Zhang

Wang²,

Pan³

et al. 2022

Front. Cardiovasc. Med.

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QT interval prolongation and ventricular arrhythmias (VAs) induced by osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, are life-threatening complications. However, no consensus has been achieved regarding their management. Overdrive pacing has been shown to be effective in shortening the QT interval and terminating torsade de pointes (TdP). Here, we report a case of osimertinib-induced QT prolongation accompanied by frequent VAs and TdP. Osimertinib was immediately discontinued after it was identified as the etiology for QT prolongation and VAs. A temporary pacemaker and overdrive pacing were used after other anti-arrhythmia treatments had failed and successfully shortened the QTc interval and terminated VAs. Repeated Holter monitoring at 1 week showed no remaining VAs or TdP, and the pacemaker was removed. Routine electrocardiography (ECG) surveillance was conducted afterward, and three- and 6-month follow-ups showed good recovery and normal ECG results. Vigilance is required for rare vital arrhythmias in patients taking osimertinib, and ECG surveillance should be conducted.

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Incidence of cardiac toxicities in patients with advanced non-small cell lung cancer treated with osimertinib: A combined analysis of two phase III randomized controlled trials

Cited by 13 publications

References 0 publications

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

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

Overdrive pacing in the acute management of osimertinib-induced ventricular arrhythmias: A case report and literature review

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