Endocrine Abstracts

Introduction: Tyrosine kinase inhibitors (TKIs) are used for treatment of iodine-refractory differentiated thyroid cancer (DTC) in patients with progressive advanced disease.Sorafenib and lenvatinib are the TKIs currently approved for this indication.

Objective: To describe the clinical experience in patients with iodine-refractory DTC treated with TKIs in our Institution.

Materials and methods: Restrospective cohort study of patients with iodine-refractory DTC who received TKIs from 2010 to 2017 in Hospital Universitario La Princesa.We included patients with available clinical data and at least one radiographic control after starting treatment with TKIs.Patients with anaplastic or medullary thyroid carcinoma were excluded.Baseline clinical characteristics, evolution, objective response to treatment, tolerability and adverse events(AE) were collected.Data were analyzed by descriptive statistics with G-Stat 2.0.1.

Results: Twelve patients were included. Mean age at diagnosis was 54(SD13.7) years, (83.3% women). Histhologic diagnosis: 7 papillary thyroid cancer, 4 poorly differentiated follicular thyroid cancinoma and 1 Hürtlhe cell cancer. Distant metastasis at diagnosis were present in 25% of patients. In the other 75% median time to metastasis diagnosis was 24(IQR12) months. Seven patients had more than one metastatatic lesion site. Median time from diagnosis of distant metastasis to TKIs initiation was 24(IQR78) months. Sorafenib, lenvatinib and sunitinib were used as first-line treatment in 8, 2 and 2 patients respectively. First radiographic control was performed at 5.33 (SD2.7) months after start of treatment and showed partial response(PR), stable disease(SD), complete response(CR) and progressive disease(PD) in 5(41.67%), 1 (8.33%), 1(8.33%) and 5(41.67%) patients respectively, with an objective response rate of 58.3%. The only CR was seen on first-line lenvatinib. Before radiographic control 2 patients required a second-line treatment with sorafenib and sunitinib each, due to intolerability. AE occurred in all patients. The most common were fatigue/hyporexia (83.3%) followed by cutaneous AE (58.3%), diarrhea (41.6%), hypertension (16.6%) and mucositis (16.6%). Cutaneous AE ocurred only with sorafenib. The rest of AE were collected for all TKIs (including one case of grade 3 mucositis with Lenvatinib). All patients eventually required dose reductions due to toxicity. Definitive withdrawal was necessary in 83.33% of patients, 50% due to toxicity and 33.33% due to progressive disease. Mortality related to cancer occurred in 8 patients, with a median time of 18 (IQR36) months after start of TKIs.

Conclusion: In our study, use of TKIs showed a similar clinical response to reported in literature with sorafenib. AE are common, being necessary a multidisciplinary management of this treatment in specialized centers.