Redifferentiation Effect of Larotrectinib for <i>NTRK</i> Fusion-Positive Pediatric Thyroid Cancer and Outcomes After Therapy

Abstract

Abstract Context Few data exist regarding larotrectinib therapy in pediatric NTRK 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 NTRK fusion–positive pediatric PTC and RAIR pulmonary metastases treated with larotrectinib and considered for 131I 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 123I thyroid scans, any RAI uptake was identified in only 2 patients, and therapeutic 131I 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 NTRK fusion-positive PTC, therapy with 131I 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.

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