Lenvatinib therapy in progressive, radioiodine-refractory, differentiated thyroid carcinoma: analysis of 74 cases followed in a single centre

Objectives: Lenvatinib is an oral multi-thyrosine kinase inhibitor (TKI) approved for the treatment of progressive radioiodine-refractory differentiated thyroid carcinoma (DTC). Primary endpoint was to confirm, in the clinical practice, the efficacy of Lenvatinib therapy in a big series of patients followed in a single centre; secondary endpoint was to evaluate its safety. Methods: we analyzed the clinical, biochemical and pathological data of 74 patients who, for progressive DTC according to RECIST 1.1, started Lenvatinib therapy. Results: in our study group no epidemiological, clinical and pathological differences have been found respect the SELECT study (median age at diagnosis 65.5 vs 64 years; male ratio 51% vs 48%; prior treatment with other TKI in 28% vs 25%; presence of lung metastases in 89% vs 87%). At the moment of first control, after a median of 2 months of Lenvatinib therapy, 100% of patients had e clinical benefit: 34% had a partial response (PR) and 66% had a stable of disease (SD). After a mean of 16 months of follow-up, 30/74 (40.5%) patients were still being treated: 14/30 (47%) patients remained in PR; 12/30 (40%) patients remained in SD, 4/30 (13%) had a progressive disease (PD). We noticed not only a radiological response but also a decreasing in serum thyroglobulin (Tg) value or in the titer of anti-Tg antibodies (TgAbs): at the screening, the median Tg value was 452 ng/ml and the median titer of TgAbs was 193 U/ml vs the median Tg value of 219 ng/ml and the median titer of TgAbs of 54 U/ml at the moment of the best response. Treatment-related adverse events (AE) occurred in 93% of patients. The most frequent AE were fatigue (81%), nausea and anorexia (74%), weight loss (68%), arterial hypertension (67%), dysgeusia (45%), diarrhea (33%) and proteinuria (20%). Regarding the AE, a mean of 84% of patients had grade1/2 AE according to the Common Terminology Criteria for Adverse Events (CTCAE) and only 14% of patients had grade 3/4 (AE). Five/39 deaths, occurred during Lenvatinib therapy, were most likely considered to be drug-related. Conclusions: these data confirmed that, in the clinical practice, Lenvatinib therapy is effective and associated with a progression-free survival similar to that reported in the phase III SELECT study. After 16 months of follow-up the global response rate was of 40.5%. A high percentage of patients developed AE drug-related but mainly of low-medium grade.