Larotrectinib Before Initial Radioactive Iodine Therapy in Pediatric TRK Fusion–Positive Papillary Thyroid Carcinoma: Time to Reconsider the Treatment Paradigm for Distantly Metastatic Disease?

Waguespack, Steven G.; Tewari, Sanjit O; Busaidy, Naifa L.; Zafereo, Mark

doi:10.1200/po.21.00467

Cited by 15 publications

(5 citation statements)

References 23 publications

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“…Several studies have shown that by inhibiting MAPK signaling with mutation-specific kinase inhibitors, RAI uptake can be restored, allowing subsequent I 131 therapy in a tumor which was previously non-RAI avid. Redifferentiation therapy has been attempted using MEK inhibitors in RAS-mutant tumors (141)(142)(143)(144)(145), BRAF ± MEK inhibitors in BRAFV600E-mutant tumors (142,143,(146)(147)(148)(149), and even NTRK or RET inhibitors in patients harboring corresponding fusions (150)(151)(152)(153). Data thus far show promising results with this strategy, allowing disease control in many patients and potentially delaying the need for systemic therapy with kinase inhibitors.…”

Section: Differentiated Thyroid Cancermentioning

confidence: 99%

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy

Turner,

Hamidi,

Ouni

et al. 2024

Front. Immunol.

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Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also been thoroughly studied and has shown promise in selected cases. In this review, we summarize the progress in the understanding of the genetic landscape and the cellular and molecular basis of radioiodine refractory-DTC and ATC, as well as discuss the current treatment options and future therapeutic avenues.

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Section: Differentiated Thyroid Cancermentioning

confidence: 99%

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy

Turner,

Hamidi,

Ouni

et al. 2024

Front. Immunol.

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“…Another case series reported 2 pediatric cases, and documented a case of re-differentiation with selpercatinib targeting a RET fusion gene in metastatic RAI-resistant papillary thyroid cancer (Groussin et al, 2021). Interestingly, in one of the pediatric case report of metastatic papillary thyroid carcinoma, larotrectinib was shown to induce redifferentiation when given in the neoadjuvant setting prior to RAI, thereby achieving an improved outcome (Waguespack et al, 2022b). Prospective studies using such targeted agents are needed to confirm these findings and further expand the options to restore radioiodine uptake in RAI-resistant thyroid cancers.…”

Section: Re-sensitization To Rai Therapy Through Ret and Ntrk Inhibitionmentioning

confidence: 99%

Kinase inhibitors in thyroid cancers

et al. 2023

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Objective: The treatment landscape for thyroid cancers has changed rapidly with the availability of kinase inhibitors against VEGFR, BRAF, MEK, NTRK, and RET. We provide an up-to-date review of the role of kinase inhibitors in thyroid cancer and discuss upcoming trials. Design and Methods: A comprehensive review of the available literature describing kinase inhibitors in thyroid cancer was performed. Results and Conclusions: Kinase inhibitors have become the standard of care for patients with metastatic radioactive iodine-refractory thyroid cancer. Short-term treatment can re-sensitize differentiated thyroid cancer to radioactive iodine, thereby improving outcomes and sparing toxicities associated with long-term use of kinase inhibitors. The approval of cabozantinib as salvage therapy for progressive radioactive iodine-refractory differentiated thyroid cancer following failure with sorafenib or lenvatinib adds to the available armamentarium of active agents. Vandetanib and cabozantinib have become mainstay treatments for metastatic medullary thyroid cancer regardless of RET mutation status. Selpercatinib and pralsetinib, potent and selective receptor kinase inhibitors with activity against RET have revolutionized the treatment paradigm for medullary thyroid cancers and other cancers with driver mutations in RET. Dabrafenib plus trametinib for BRAF mutated anaplastic thyroid cancer provides an effective treatment option for this aggressive cancer with a dismal prognosis. In order to design the next generation of agents for thyroid cancer, future efforts will need to focus on developing a better understanding of the mechanisms of resistance to kinase inhibition including bypass signaling and escape mutations.

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“…[37][38][39] In addition, both laboratory studies and case reports have highlighted the potential for targeted therapy to induce differentiation of PTC, increasing expression of the sodium iodine symporter (NIS) and radioiodine uptake. [40][41][42][43][44][45][46][47] Building on these findings, we have established a task force including endocrinologists and surgeons to consider the feasibility of conducting a study to evaluate neoadjuvant targeted therapy to decrease surgical morbidity and/or increase sensitivity to RAI therapy and hope to leverage the COG/National Cancer Institute (NCI) Molecular…”

Section: Thyroid Carcinomamentioning

confidence: 99%

“…The inclusion of patients with thyroid cancer on basket trials of RET and TRK inhibitors has demonstrated high levels of activity of these agents and resulted in FDA approval of multiple oncogene‐specific targeted therapies for patients with RAI‐refractory disease 37–39 . In addition, both laboratory studies and case reports have highlighted the potential for targeted therapy to induce differentiation of PTC, increasing expression of the sodium iodine symporter (NIS) and radioiodine uptake 40–47 . Building on these findings, we have established a task force including endocrinologists and surgeons to consider the feasibility of conducting a study to evaluate neoadjuvant targeted therapy to decrease surgical morbidity and/or increase sensitivity to RAI therapy and hope to leverage the COG/National Cancer Institute (NCI) Molecular Characterization Initiative (MCI) to profile tumors.…”

Section: Introductionmentioning

confidence: 99%

Children's Oncology Group's 2023 blueprint for research: Rare tumors

Schultz

Chintagumpala

Piao

et al. 2023

Pediatric Blood & Cancer

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The Children's Oncology Group (COG) Rare Tumor Committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid tumors that do not fall within another COG disease committee. Current therapeutic trial development focuses on nasopharyngeal carcinoma, adrenocortical carcinoma, pleuropulmonary blastoma, colorectal carcinoma, melanoma, and thyroid carcinoma. Given the rarity of these tumors, novel strategies and international collaborative efforts are necessary to advance research and improve outcomes.

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Larotrectinib Before Initial Radioactive Iodine Therapy in Pediatric TRK Fusion–Positive Papillary Thyroid Carcinoma: Time to Reconsider the Treatment Paradigm for Distantly Metastatic Disease?

Cited by 15 publications

References 23 publications

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy

Kinase inhibitors in thyroid cancers

Children's Oncology Group's 2023 blueprint for research: Rare tumors

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