Redifferentiation Effect of Larotrectinib for Fusion-Positive Pediatric Thyroid Cancer and Outcomes After Therapy.

[CONTEXT] Few data exist regarding larotrectinib therapy in pediatric fusion-positive papillary thyroid cancer (PTC), especially its effects on redifferentiation in radioactive iodine-refractory (RAIR) disease.

[OBJECTIVE] To describe redifferentiation effects and disease outcomes in patients with stage 2 pediatric PTC following treatment with larotrectinib ± RAI.

[METHODS] A retrospective case series at a tertiary cancer center of patients with fusion-positive pediatric PTC and RAIR pulmonary metastases treated with larotrectinib and considered for I therapy. Tumor response was assessed utilizing RECIST 1.1.

[RESULTS] Four patients (aged 6-16 years at PTC diagnosis; 50% female) were treated with larotrectinib 100 mg twice a day for a median of 14 months (range 6-30 months). Treatment was well tolerated, except for grade 3 hypocalcemia in 1 patient with pre-existing hypoparathyroidism. All patients had tumor shrinkage (-25% to -100%) in target and nontarget pulmonary metastases. On diagnostic I thyroid scans, any RAI uptake was identified in only 2 patients, and therapeutic I did not cause further incremental tumor shrinkage in the patients treated, despite robust pulmonary uptake on the post-therapy scans. After stopping larotrectinib and with a mean follow-up of 38 months (range 26-48 months), 2 patients had stable disease and 2 had clinically insignificant tumor progression.

[CONCLUSION] Although larotrectinib can have a redifferentiation effect in pediatric fusion-positive PTC, therapy with I may not lead to an incremental benefit in established RAIR disease. Significant structural disease progression did not occur after cessation of larotrectinib, suggesting that a drug holiday can safely be considered in this population.