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

Abstract

Objective: 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.

Design/methods: 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).

Results: 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%).

Conclusion: 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.

Keywords: lenvatinib; radio-iodine refractory; thyroid cancer; tyrosine kinase inhibitors.

Figure 1

Bar graph of 8-week lenvatinib dose distribution in patients who commenced lenvatinib 24 mg daily. Adv-DTC, advanced differentiated thyroid cancer; PDTC, poorly differentiated thyroid cancer; PTC, papillary thyroid cancer; FTC, follicular thyroid cancer.