Background: The prognosis of several human
malignancies has dramatically improved after the introduction of
tyrosine kinase inhibitors (TKIs); however, their use has been associated with a large spectrum of adverse events, including symptomatic biliary disorders. In the phase III trial of
lenvatinib in radioactive
iodine (RAI)-refractory differentiated
thyroid cancer (DTC) patients, gallbladder (GB) and biliary duct (BD) diseases and complications were reported. We evaluated symptomatic biliary disorders during treatment with
lenvatinib in real-life practice to provide a more exhaustive understanding of its toxicity. Methods: We retrospectively evaluated all consecutive patients treated with
lenvatinib in our center for progressive RAI-refractory DTC, excluding those who underwent
cholecystectomy before the start of
therapy. We report all radiologically confirmed symptomatic GB/BD disorders, which were subsequently treated with
cholecystectomy, and we describe their management along with relevant biochemical and histological findings. All available GB/BD imaging of patients who developed biliary toxicity during
lenvatinib was reviewed by a single experienced radiologist, including computed tomography scans performed for
tumor assessment at baseline and during TKI
therapy. Results: Five patients (14.7%) developed symptomatic radiologically confirmed biliary disease after a median time of 4.4 months of
lenvatinib treatment [interquartile range 3.4-14.4 months] and thus underwent
cholecystectomy. A scheduled surgical approach was possible only in two cases; in the remaining patients, presurgical TKI interruption was shorter than one week. After wound healing, treatment was resumed by all subjects. Three patients showed mild biochemical alterations in the two previous monthly follow-up visits. Before the start of treatment, GB/BD abnormalities were radiologically detected only in one case. Conclusions: In our cohort, an unexpectedly high proportion of RAI-refractory DTC patients treated with
lenvatinib developed a symptomatic biliary disorder with the need of surgical intervention. Further studies are required to optimize the diagnosis and treatment of patients at higher risk of developing a symptomatic GB/BD disease during assumption of
lenvatinib.