Response to Lenvatinib in Children with Papillary Thyroid Carcinoma

Abstract

Lenvatinib therapy is well tolerated and demonstrated clinical activity in children with advanced PTC. Lenvatinib should be considered in children with PTC that is refractory or not amenable to conventional management.

Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma

“…Sorafenib has been studied in a phase 2 trial in pediatrics but no PTC patients were enrolled on study 45 . A recent report of three pediatric patients with refractory PTC who demonstrated clinical improvement with lenvatinib suggests that this may also be of potential utility in relapsed or refractory patients 46 . Additionally, selpercatinib, an oral and selective investigational drug targeting RET kinase abnormalities, was recently FDA approved for patients ages 12 and older with metastatic or advanced RET ‐mutated medullary thyroid carcinoma or RET fusion–positive (and RAI‐refractory) thyroid cancer 47 .…”

Thyroid Cancer in the Pediatric Population

“…In the setting of adult late-stage metastatic and progressive radioactive iodine-refractory differentiated thyroid carcinoma, sorafenib and lenvatinib have both shown improved progression free survival compared to placebo, 10.8 months vs. 5.8 months (hazard ratio 0.59) and 18.3 months vs. 3.6 months (hazard ratio 0.21) respectively [116,119,120]. In the pediatric population, response to sorafenib has been reported both in progressive RAI refractory PTC, PTC with diffuse metastatic disease not amenable to upfront RAI, and as gap therapy in a patient who could not receive RAI in a timely fashion (one case each) [121,122,123], while stable disease has been reported in three pediatric patients with extensive bilateral metastatic pulmonary disease treated with lenvatinib (including one previously treated with sorafenib) [124]. Clinical trials evaluating the efficacy of lenvatinib in the treatment of children with refractory or relapsed solid malignancies (including thyroid cancer) are ongoing.…”

“…The two pediatric patients included in this cohort did not have measurable disease at the time of the trial; they remained stable on therapy at 16 months [130,131,132]. An additional case of pediatric thyroid cancer with TRK-inhibitor induced stabilization of disease was reported by Mahajan et al [124]. Studies evaluating the efficacy of ALK inhibitors for tumors outside of ALK -rearranged non-small cell lung cancer (including thyroid cancer) are also underway [133], with a case report in the adult population demonstrating an excellent response to crizotinib (>90% reduction of pulmonary disease) [134].…”

Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology

“…A case report described three patients with papillary thyroid carcinoma who were successfully treated with lenvatinib. 60 Two out of three patients remained stable for 11 months after start of lenvatinib. A model-based analysis of adult PK-PD data showed a correlation between lenvatinib AUC 0-24h and reduction in tumor size, but a threshold to guide TDM was not reported.…”