Predictors of response to lenvatinib in advanced differentiated thyroid cancer: focus on the CONUT score

Lenvatinib is a multityrosine kinase inhibitor approved for progressive radioiodine refractory differentiated thyroid cancer (RAI-R-DTC). Despite its efficacy, most of the initial experiences showed global inferior results if compared with SELECT study. Baseline disease stages, previous systemic treatments and baseline patients' characteristics may affect response to therapy. The aim of our study was to review relevant clinical outcomes, identifying survival predictors, of a single center cohort of patients with advanced thyroid cancer treated with Lenvatinib.

Twenty-two patients with progressive RAIR-R-DTC treated with Lenvatinib were retrospectively included. For each patient, we reviewed the main clinical baseline characteristics, including nutritional status. We evaluated the latter by using CONtrolling NUTritional status (CONUT) score. Clinical outcomes were overall survival (OS) and progression free survival (PFS).

At the time of analysis, 14 patients (63.6%) were alive with a median OS of 54 months (95% CI 20.35-87.65 months). Progression occurred in 16 patients (72.7%) with a median PFS of 21 months (95% CI 0-47.33 months). Nineteen out of 22 patients (86.4%) presented at least one adverse event (AE) of any grade. Baseline lower CONUT score significantly correlated with both longer PFS (HR 2.77- 95% CI 1.216-6.307, p = 0.015) and longer OS (HR 4.455-95% CI 1.211-16.391, p = 0.025). A significant longer survival was observed in patients with ECOG 0 compared to those with ECOG 1 and in the latter compared to ECOG 2 group (Log-rank test: p = 0.040). Conversely, higher baseline ECOG Performance Status (PS) correlated with higher severity of AEs (rs 0.468, p = 0.027). Finally, responder patients showed a significantly better PFS (HR 2.337-95% CI 1.091-5.006, p = 0.029).

We confirmed the good efficacy of Lenvatinib treatment in progressive advanced RAI-R-DTCs showing the prognostic value of best tumor response, ECOG PS and CONUT score.