Real-world efficacy of lenvatinib/pembrolizumab combination in anaplastic thyroid carcinoma: case series from two Italian referral centers

Objective: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive cancer, traditionally refractory to conventional treatments. The combined therapy with lenvatinib and pembrolizumab (L + P) is supported by a preclinical rationale based on the distinctive immunological profile of ATC. We propose a real-life study to evaluate relevant clinical outcomes and identify survival predictors in a cohort of ATC patients treated with the combined therapy in two Italian referral centers. Methods: Sixteen ATC patients treated with the combination of L + P were retrospectively included. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed according to RECIST 1.1 criteria. Baseline patient characteristics, including immuno-nutritional status (calculated using the CONUT score), were analyzed to identify potential predictors of response. Results: A median OS of 10 months (95% CI: 4.2-15.9 months) and a median PFS of 6.0 months (95% CI: 0-12.7 months) were observed after L + P therapy. Complete response was observed in 6.2% and partial response in 31.3% of patients, resulting in an ORR of 37.5%; the DCR was 68.8%. Progressive disease occurred in 25% of patients. Furthermore, a baseline CONUT score ≤ 2 resulted in a significantly longer OS (log-rank, P = 0.001) and PFS (P = 0.05) compared to CONUT score ≥ 3, while a non-significantly longer OS was observed between patients with a baseline ECOG PS of 0-2 and those with a baseline ECOG PS ≥ 3. Conclusion: Our study confirms the efficacy and safety of L + P therapy, identifying the CONUT score as a prognostic factor.