Aims
Lenvatinib is a multi-targeted tyrosine kinase inhibitor approved for treatment of metastatic radioiodine-refractory thyroid cancer. Phase III clinical trials demonstrated improved progression-free survival. However, real-world data has raised concerns regarding tolerability of lenvatinib’s 24mg starting dose and efficacy. We aimed to assess outcomes of lenvatinib in an Australian practice setting.
Methods
We performed retrospective analysis of thyroid cancer patients on lenvatinib at a quaternary referral centre from 2010-2023. Medical records were searched for demographic data, tumour details, treatment-related adverse effects (TRAEs), biochemical and radiological response.
Results
64 patients were included (33% papillary, 22% insular, 16% medullary, 9% Hurthle, 8% follicular, 6% anaplastic, 6% mixed pathology). 20% of cases were BRAF mutated. Median age at diagnosis was 59 years old (range 28-90). 53% were female. Most common sites of metastases included lung (76%), skeletal (37%) and liver (12%).
Lenvatinib starting doses were 24mg (n=48, 75%), 20mg (n=4), 10mg (n=1) and unknown (n=11). 21 out of 48 patients (44%) remained on 24mg at 8 weeks. In the entire cohort, common TRAEs included hypertension (n=36), proteinuria (n=10), fatigue (n=33), nausea (n=18) and palmar-plantar erythrodysesthesia (n=9). Three patients discontinued lenvatinib due to significant TRAEs.
In a subset of 35 patients with follicular cell-derived thyroid cancer, 15 patients (43%) had analysable baseline and follow-up thyroglobulin levels. Median baseline thyroglobulin was 320 ug/L(range 10.8-13500) and nadir was 14.9 ug/L(range 1.2-1910). Median reduction in thyroglobulin was 91.3%(range 62.2%-99%). Best disease response as per RECIST criteria was available for 17 out of 35 patients (49%). 6 (35%) achieved partial response, 10 (59%) sustained stable disease and one (6%) had progressive disease.
Conclusion
Our study demonstrates lenvatinib is effective for radioiodine-refractory thyroid cancer but fewer than 50% reach 8 weeks at full dose. Our cohort’s reported TRAEs corresponds to prior studies, requiring supportive care to maximise efficacy.