Comprehensive assessment of multi-kinase inhibitor therapy outcomes in RAIR-(P)DTC and MTC at a tertiary referral centre.

Objective: Multi-kinase 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 centres and multicentre registries or clinical studies. Moreover, MKI efficacy in poorly differentiated thyroid cancer (PDTC) is underreported.

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

Results: 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), 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 = 0.039; HR, 2.34, p = 0.031). 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 = 0.045).

Conclusions: 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-centre management compared to prior trials and real-world data.