Real-world data show limited efficacy of sequential cabozantinib treatment in RAIR-(P)DTC.

Cabozantinib has significantly improved progression-free survival (PFS) in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) after lenvatinib and/or sorafenib pretreatment in the phase 3 COSMIC-311 trial, leading to its approval for sequential treatment. Real-world evidence of cabozantinib remains limited, particularly in poorly differentiated thyroid cancer (PDTC). In this retrospective analysis, we included adult patients with RAIR-DTC or PDTC treated with cabozantinib as further-line treatment at the Essen Endocrine Tumor Center (June 2022-July 2025). All patients had received prior targeted therapy and had documented progressive disease at cabozantinib initiation. Best overall response, PFS, overall survival (OS) and adverse events were assessed. Nineteen patients (7 DTC and 12 PDTC) were included in the safety analysis, and 17 patients were included in the efficacy assessment. Under sequential cabozantinib treatment, partial response (PR) was observed in 4/17 (24%): 3/4 in patients switched due to lenvatinib toxicity and 1/13 in those switched due to progression. Median PFS was 5.4 months in DTC and 3.6 months in PDTC. Median OS from cabozantinib initiation was 13.5 months in DTC and 15.8 months in PDTC. Dose reductions or interruptions were required in 6/19 (31.6%), and 3/19 (15.8%) permanently discontinued cabozantinib due to toxicity. In this real-world cohort, further-line cabozantinib showed limited efficacy in RAIR-(P)DTC, especially in PDTC. Responses were more favorable when cabozantinib was initiated due to prior treatment toxicity rather than progression. The substantial toxicity highlights the need for careful management and improved therapeutic strategies in this population.