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Acute left ventricular dysfunction induced by a panHER and VEGFR tyrosine kinase inhibitor in a phase I trial
Rastislav Bahleda1, Christophe Massard, Jean-Charles Soria
1Département de Médecine, Service des Innovations Thérapeutiques Précoces, Institut Gustave Roussy, Université Paris XI, Villejuif, France.
Abstract:
Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or VEGFR receptors have demonstrated substantial clinical benefit in patients with advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung cancer, and renal cell carcinoma. Nevertheless, these drugs have some target related adverse effects, particularly cardiovascular toxicities. We report here the case of a patient included in a phase I trial of a new compound, a tyrosine kinase inhibitor targeting HER1, HER2, HER4 and VEGFR2. The patient developed during this treatment an acute and transient left ventricular systolic dysfunction. Careful management of this adverse effect allowed the patient to continue therapy and to achieve a major partial response.
Insights
New tyrosine kinase inhibitors (TKI) show promise for advanced cancers but can cause cardiovascular toxicities. Careful management of left ventricular systolic dysfunction enabled a patient to continue treatment and achieve a major partial response.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKI) and monoclonal antibodies targeting EGFR, HER2, and VEGFR receptors offer significant clinical benefits for various advanced cancers.
- However, these targeted therapies are associated with specific adverse effects, notably cardiovascular toxicities.
Observation:
- A patient in a phase I trial received a novel tyrosine kinase inhibitor targeting HER1, HER2, HER4, and VEGFR2.
- The patient experienced acute and transient left ventricular systolic dysfunction during treatment.
Findings:
- The observed left ventricular systolic dysfunction was successfully managed.
- This management allowed the patient to continue the investigational therapy.
Implications:
- Effective management of cardiovascular toxicities is crucial for patients undergoing treatment with multi-targeted TKIs.
- This case highlights the potential for continued therapy and positive clinical outcomes despite treatment-related adverse events.
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