Redifferentiating Effect of Larotrectinib in NTRK -Rearranged Advanced Radioactive-Iodine Refractory Thyroid Cancer

• Published in: Thyroid (New York, N.Y.) Vol. 32; no. 5; p. 594
• Main Authors: Groussin, Lionel, Theodon, Hélène, Bessiene, Laura, Bricaire, Leopoldine, Bonnet-Serrano, Fidéline, Cochand-Priollet, Béatrix, Leroy, Karen, Garinet, Simon, Pasmant, Eric, Zerbit, Jérémie, Seban, Romain, Goldwasser, François, Clerc, Jérôme, Cottereau, Anne Segolene, Huillard, Olivier
• Format: Journal Article
• Language: English
• Published: United States 01-05-2022
• Subjects: Adult; Child; Humans; Iodine - therapeutic use; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - genetics; Thyroid Neoplasms - radiotherapy; radioactive iodine resistance; larotrectinib; NTRK; redifferentiation; differentiated thyroid cancer
• ISSN: 1557-9077
• DOI: 10.1089/thy.2021.0524

Metastatic thyroid cancers may dedifferentiate and become radioactive-iodine (RAI) resistant. A redifferentiating effect can be observed with inhibitors of the mitogen-activated protein kinase pathway in thyroid cancers with point mutation in oncogenes. This effect allows RAI reuptake that may lead to a therapeutic effect different from the antitumoral effect of the inhibitor. The potential redifferentiating effect of inhibitors targeting oncogenic fusion-genes was suggested by one adult and one pediatric patient using larotrectinib in
-rearranged tumors. We report on three consecutive adult patients with metastatic RAI-resistant
rearranged thyroid cancer who received larotrectinib for disease progression and for whom the redifferentiating effect was examined. Larotrectinib-induced RAI reuptake in all or part of the metastatic disease for two patients and no reuptake was noted for the other patient. We demonstrate that redifferentiation of
-rearranged RAI-resistant thyroid cancer with larotrectinib may exist but does not occur in all patients.