Tyrosine kinase inhibitors rechallenge in solid tumors: a review of literature and a case description with lenvatinib in thyroid cancer

ABSTRACT

Introduction: In the last decade tyrosine kinase inhibitors (TKIs) have been employed for a wide range of hematological and solid tumors and today they represent a valid therapeutic option for different neoplasms. Among them, both sorafenib and lenvatinib were approved for the treatment of radioactive iodine (RAI) refractory differentiated thyroid carcinoma (DTC). Unfortunately, in some cases the efficacy of TKIs is limited by the onset of drug resistance after the initial response.

Areas covered: We report the case of a patient with a RAI refractory advanced DTC, treated with lenvatinib after surgery, multiple RAI administrations, traditional chemotherapy, and sorafenib. During treatment with lenvatinib, a noticeable response was detected by sequential computed tomography scans but, after 27 months, tumor progression became evident and led to lenvatinib interruption. In absence of any active treatment, a further disease progression was documented, and lenvatinib was re-administered obtaining a new objective response. Starting from this case report, we review available reports about the rechallenge with TKIs in solid tumors, discussing the possible mechanisms underlying the efficacy of this approach.

Expert commentary: Rechallenge with TKIs in solid tumors could be a therapeutic option in subjects with advanced and metastatic DTC who experience a progressive disease after initial response to lenvatinib.

KEYWORDS:

• Differentiated thyroid carcinoma
• drug-resistance
• lenvatinib
• rechallenge
• tyrosine-kinase inhibitors

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed that they have received honoraria as a principal investigator from Amgen, Bayer Health Care, Eisai, Exelixis, Oxygene, Pfizer, Sanofi-Genzyme Ipsen, and Novartis. They are also a member of Astra-Zeneca and Sobi Advisory Boards. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

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Funding

Editorial assistance for the preparation of this manuscript was provided by Luca Giacomelli, PhD, on behalf of Content Ed Net; this assistance was funded by Eisai. The sponsoring company was not offered the opportunity to revise the manuscript and had no role in the decision to submit.