Comprehensive Assessment of Multikinase Inhibitor Therapy Outcomes in RAIR-(P)DTC and MTC at a Tertiary Referral...

Multikinase inhibitors (MKIs) have transformed treatment for advanced radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and medullary thyroid cancer (MTC). However, limited insight exists into management differences between expert centers and multicenter registries or clinical studies. Moreover, MKI efficacy in poorly differentiated thyroid cancer (PDTC) is underreported.

This retrospective analysis included 154 patients with thyroid cancer (51 PDTC, 49 DTC, 54 MTC) treated with MKIs from 2011 to 2024 at the Essen Endocrine Tumor Center by a consistent specialist team. Clinical characteristics, tumor genetics, time to treatment, and treatment outcomes were assessed. Cox regression analyses identified prognostic survival factors.

In (P)DTC, lenvatinib showed higher objective response rate (ORR) (64% vs 18%) and longer median progression-free survival (PFS) (22.4 vs 6.7 months) than sorafenib, especially in PDTC (21.2 vs 3.5 months). Lenvatinib-treated patients without bone metastases had higher ORR (74% vs 53%), while higher age and liver metastases were associated with shorter PFS (HR, 2.12, P = .039; HR, 2.34, P = .031). In MTC, vandetanib demonstrated higher ORR (60% vs 18%) and longer PFS (26.1 vs 10.0 months) than cabozantinib. Vandetanib as first-line showed higher ORR (67% vs 25%) and RET mutations correlated with longer PFS (HR, 0.14, P = .045).

Lenvatinib outperformed sorafenib, particularly in PDTC, suggesting the need for alternative treatments. In MTC, vandetanib was more effective than cabozantinib, supporting its use as first-line therapy. However, the choice of MKI was determined by the treating physician. Our data highlight MKI effectiveness under expert-center management compared to prior trials and real-world data.