Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review

Objective The aim of this article is to conduct a literature review on first-generation TRK inhibitors (TRKi), namely entrectinib and larotrectinib, to describe the most common adverse events (AEs) and their management in adults. Methods A search strategy was conducted in MEDLINE, EMBASE, and Google...

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Bibliographic Details
Published in:Supportive care in cancer 2022-12, Vol.30 (12), p.10471-10482
Main Authors: Martineau, Christine, Turcotte, Maria-Kim, Otis, Noémie, Provost, Frédéric, Themens, Ludovic, Guay, Marie-Pascale, Letarte, Nathalie, Adam, Jean-Philippe
Format: Article
Language:English
Subjects:
Adults
Cancer therapies
Genetics
Inhibitor drugs
Kinases
Medicine
Medicine & Public Health
Nursing
Nursing Research
Oncology
Pain Medicine
Pharmacology
Phenols
Rehabilitation Medicine
Review Article
Side effects
Taste disorders
Tyrosine
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Summary:Objective The aim of this article is to conduct a literature review on first-generation TRK inhibitors (TRKi), namely entrectinib and larotrectinib, to describe the most common adverse events (AEs) and their management in adults. Methods A search strategy was conducted in MEDLINE, EMBASE, and Google Scholar using a list of predetermined keywords. Peer-reviewed articles written in English and published through June 2021 were included. Articles covered included randomized clinical trials and expert recommendations, as well as patent and other types of reviews. Results The discussed AEs include weight gain and withdrawal pain, as well as neuromuscular, central nervous system (dysesthesias and peripheral sensory neuropathies, dizziness and ataxia, and dysgeusia), gastrointestinal (nausea, vomiting, and diarrhea), and respiratory symptoms. Additionally, several AEs encountered with entrectinib specifically (cognitive and vision disorders, congestive heart failure, QTc elongation, and skeletal fractures) are discussed. First, an overall mechanism of action explaining these AEs is presented. Then, for each AE, incidence and severity are stated and followed by practical management recommendations. While nearly all AEs were reversible upon TRKi suspension, the proposed managements are mainly constituted of pharmacological and non-pharmacological interventions. Conclusion With the estimated growth of gene sequencing in the coming years, it is foreseeable that TRKi will take a larger position in the oncologic therapeutic arsenal. Therefore, adequate management of AEs associated with TRKi in adults should be a prime focus.
ISSN:0941-4355
1433-7339
DOI:10.1007/s00520-022-07401-y