Did selective kinase inhibitors change the management of patients with radioiodine-refractory thyroid cancer?

Abstract

Objective: To analyse at our institution the criteria for selecting a first-line therapy for patients with advanced radioiodine-refractory thyroid cancer and their clinical responses, safety and survival outcomes.

Patients and methods: We extracted data from 69 consecutive patients referred to Federico II University Hospital from September 2016 to September 2024, among whom 44 patients were treated with TKIs as first-line treatment and outside any clinical trial, and form the basis of this report.

Results: Thirty-one (71%) patients were treated with the antiangiogenesis inhibitor lenvatinib and 13 (29%) were treated with selective tyrosine kinase inhibitors (s-TKIs). Among the latter, eight patients were treated with dabrafenib + trametinib (DT), two patients were treated with selpercatinib because of contraindications to lenvatinib, and three patients received DT as redifferentiation therapy. A RECIST partial response was observed in 28% of patients treated with lenvatinib, in 63% of those treated with DT and in one of the two patients treated with selpercatinib. Grade ≥3 adverse events occurred in 13 (42%) patients treated with lenvatinib and only in 1 (9%) patient treated with DT. Progression-free survival (PFS) and overall survival rates at 1 year were 72% and 83% in lenvatinib-treated patients and 69% and 83% in DT-treated patients, respectively. In both selpercatinib-treated patients, the PFS at data cut-off was 10 months. No treatment-related deaths were observed.

Conclusion: S-TKIs permitted tailoring systemic treatment based on disease location, tumour volume and patient comorbidities, achieving satisfactory tolerance and outcomes in selected patients with an actionable driver mutation and with contraindications to angiogenesis inhibitors or candidates for redifferentiation therapy.

Keywords: advanced thyroid cancer; differentiated thyroid cancer; first-line treatment; selective kinase inhibitors; tyrosine kinase inhibitors.

Figure 1

(A, B). Kaplan-Meier curve of progression-free survival (A) and overall survival (B) from the time of treatment initiation with lenvatinib. 95% CI is reported with a dotted line. (C) Waterfall plot of the best RECIST changes. Red, progressive disease; yellow, stable disease; and green, partial response.

Figure 2

Treatment duration and time to events in the eight patients who received dabrafenib + trametinib on a continuous basis. The green bars correspond to individual patients who achieved a partial response, and the yellow bars to individual patients who achieved stable disease. The black dots are positioned at the time of best RECIST treatment response. The dashed vertical line marks the 1-year time point.

Figure 3

Representative images of two patients who achieved a partial response of >12 months with dabrafenib + trametinib. (A–D) The first patient had global disease progression with the appearance of a rapidly growing lymph node at the right IIB level (A, arrow) and multiple bilateral lung lesions, some of which are shown in C (arrow). Twelve months after starting treatment, the neck lesion was no longer visible (B), as were most of the lung metastases (D). (E, F) The second patient presented with a paratracheal lesion with intense uptake on the ¹⁸FDG-PET (E, arrow) and pulmonary metastases (not shown). After 13 months of treatment, the paratracheal lesion showed the greatest volumetric reduction (F, arrow) and was associated with a complete response in the lungs (not shown).