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

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Abstract

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.

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Author information

Author notes

  1. Christine Martineau, Maria-Kim Turcotte, Noémie Otis, Frédéric Provost, and Ludovic Themens contributed equally to this work.

Authors and Affiliations

  1. Faculty of Pharmacy, Université de Montréal, Montréal, Canada

    Christine Martineau, Maria-Kim Turcotte, Noémie Otis, Frédéric Provost, Ludovic Themens & Nathalie Letarte

  2. Department of Pharmacy, CIUSSS West-Central Montreal, Montréal, Canada

    Marie-Pascale Guay

  3. Department of Pharmacy, Centre hospitalier de l’Université de Montréal, 1050 Sanguinet, Montréal, H2X 0C1, Canada

    Nathalie Letarte & Jean-Philippe Adam

  4. CHUM Research Center, CHUM, Montréal, Canada

    Nathalie Letarte & Jean-Philippe Adam

Authors
  1. Christine Martineau
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Contributions

CM, MKT, NO, FP, and LT wrote the manuscript. MPG, NL, and JPA reviewed the manuscript.

Corresponding author

Correspondence to Jean-Philippe Adam.

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Martineau, C., Turcotte, MK., Otis, N. et al. Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review. Support Care Cancer 30, 10471–10482 (2022). https://doi.org/10.1007/s00520-022-07401-y

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  • DOI: https://doi.org/10.1007/s00520-022-07401-y

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