Hypertension, nausea, anorexia and weight loss were significantly associated with better progression-free survival in patients with radioiodine-Refractory Differentiated Thyroid Carcinoma treated with Lenvatinib

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 series of patients (pts) followed in a single centre; secondary endpoint was to search for good prognostic factors of improved progression-free survival (PFS). We analyzed the data of 74 pts who, for progressive DTC according to RECIST 1.1, started Lenvatinib therapy. Median age at diagnosis was 65 years; male/female ratio was 1.05; 28% of pts was previously treated with other TKI; lymphnodes, lung, bone, and liver metastases were present in 82%, 89%, 46%, and 20% of pts, respectively. At first control, 2 months after Lenvatinib starting therapy, the disease control-rate was obtained in 100% of pts: 35% had a partial response (PR) and 65% had a stable disease (SD). After a mean of 16 months of follow-up, 31/74 (42%) pts was still being treated: 15/31 (48%) pts remained in PR; 12/31(39%) pts remained in SD, 4/31 (13%) had a slowly progressive disease (PD). The best radiological response was obtained after a mean of 4 months of therapy. The median PFS and overall survival were 38 and 22 months, respectively. The treatment-related adverse events (AE) occurred in 93% of pts. The most frequent AE were fatigue (78%), nausea and anorexia (75%), weight loss (67%), arterial hypertension (67%), dysgeusia (46%), diarrhea (32%) and proteinuria (28%). Regarding the AE severity, the majority of pts had grade1/2 according to the Common Terminology Criteria for Adverse Events (CTCAE). The occurrence of hypertension or nausea-anorexia or weight loss was significantly associated with a better PFS (45 vs 19 months, p = 0.03; 45 vs 7 months, p = 0.0002; 45 vs 7 months, p < 0.0001, respectively). These data confirmed that, in clinical practice, Lenvatinib therapy is effective and associated with a prolonged PFS. After 16 months of follow-up the clinical benefit rate was 42%. In our series the occurrence of AE of hypertension, nauseaanorexia and weight loss predicted a better response.