| Summary: | <i>Background:</i> Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients with advanced thyroid cancer. <i>Methods:</i> We retrospectively evaluated 63 patients with progressive advanced thyroid carcinoma treated with TKIs divided into a Study group (23 patients) treated with salvage therapy, and a Control group (40 patients) treated with only one TKI. <i>Results:</i> Similar clinical benefits (stable disease + partial response) and progression free survival between the first and the second line TKI were observed in the Study group (<i>p</i> > 0.99 and <i>p</i> = 0.5, respectively). Median overall survival (OS) was 67.7 months in the Study group and 22.6 months in the Control group (HR 2.46; 95% CI 1.34–4.52, <i>p</i> = 0.004). After stratifying the whole population by age (<65 and ≥65 years), OS was significantly different (<i>p</i> < 0.001) with the best survival curve in younger patients, treated with salvage therapy and the worst in older subjects, treated with only one TKI. <i>Conclusions:</i> Salvage therapy showed a significant improvement of OS in patients with advanced thyroid cancer who experienced disease progression during prior TKI therapies.
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