Real-world lenvatinib use in metastatic thyroid cancer: early dose intensity and side effect profile in an Australian...

Lenvatinib is a multi-kinase inhibitor approved in radioiodine-refractory thyroid cancer based on results of a phase III trial. Real-world data have emphasised concerns regarding tolerability of the starting dose (24 mg/day) and frequency of dose-limiting treatment-related adverse effects (TRAEs). We aimed to assess early dose intensity, tolerability and efficacy using lenvatinib in metastatic thyroid cancer patients in an Australian centre.

Retrospective medical record review was conducted of patients with advanced/metastatic differentiated, medullary and anaplastic thyroid cancer on lenvatinib at a quaternary referral centre (2014-2023).

64 patients were included. Median age at lenvatinib commencement was 67 years (range 38-92). 53% were female. The most common non-nodal metastases were pulmonary (86.4%) and skeletal (50.8%). Most patients commenced lenvatinib at 24 mg/day (48/53; 90.5%), with fewer than half maintaining this dose by 8 weeks (21/45; 46.7%). Those who maintained the 24 mg dose at 8 weeks were younger at lenvatinib commencement (62 years vs 71 years, P = 0.016) and more likely to have poorly differentiated or anaplastic thyroid cancer (42 vs 22%, P = 0.018). During the median 12-month follow-up, the most common TRAEs included hypertension (n = 37), fatigue (n = 35), and nausea (n = 18). In a subgroup of 21/35 patients with differentiated thyroid cancer, median baseline and nadir serum thyroglobulin were 305 and 21.7 μg/L (median reduction 92.5% (IQR 81.1-98.0%)). In 19/35 patients with radiological response data, the majority experienced disease control as best structural response (17/19; 93.2%).

This real-world analysis demonstrates difficulties in maintaining early lenvatinib dose intensity, with frequent TRAEs. Greater emphasis on supportive care is needed to maximise early dose intensity and efficacy.