Endocrine Abstracts

JOINT1493

Background: 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. Our objective was to describe redifferentiation effects and disease outcomes in pediatric patients with stage 2 PTC following treatment with larotrectinib ± RAI.

Methods: This was a retrospective case series at a tertiary cancer center of patients <19 years with NTRK fusion-positive PTC and RAIR pulmonary metastases treated with larotrectinib and considered for ¹³¹I therapy. Tumor response was assessed utilizing RECIST 1. 1.

Results: Four patients with pediatric PTC (ages 6-16 years at diagnosis; 50% female) and lung metastases considered RAIR were treated with larotrectinib 100 mg BID for a median of 14 months (range 6-30 months). Treatment was well tolerated, except for grade 3 hypocalcemia in one patient with pre-existing hypoparathyroidism, and tumor response (-25 to -100%) occurred in all patients. On diagnostic ¹²³I thyroid scans, any RAI uptake was identified in only 2/4 patients, but therapeutic ¹³¹I did not cause an incremental tumor response in the two patients treated despite robust pulmonary uptake on the post-therapy scans. After stopping larotrectinib, all patients had stable structural disease after a mean follow-up of 38 months (range 26-48 months).

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 children with established RAIR disease. Structural disease progression does not occur after cessation of larotrectinib, suggesting that it can be safely stopped in this population.