*7.1. Immunotherapy*

In the recent years, immunotherapy has emerged as a new transformative approach into the body's natural antitumor defenses. To date, there is no approved immunotherapy for advanced thyroid cancer. A few clinical trials using novel immunotherapy agents like programmed cell death protein 1 (PD-1) checkpoint inhibitors are ongoing. Pembrolizumab in an Ib phase trial (KEYNOTE) showed a tumor size reduction of 35–50% in PTC and FTC. The use of another anti-PD1 agent (spartalizumab) was evaluated in progressive ATC that responded to therapy [161]. In an ongoing phase 2 clinical trial (NCT03246958), the efficacy of the combination of nivolumab (anti-PD1-1) and ipilimumab (anti-CTLA-4 cytotoxic T-lymphocyte-associated protein 4) was evaluated in patients with aggressive thyroid cancer. In addition, multiple clinical trials with VEGF and/or VEGF inhibitor and immune checkpoint inhibitors have been designed. Pemproblizumab plus lenvatinib was investigated in a phase 2 trial for unresectable ATC (NCT04171622) as well as in a randomized study in a small group of advanced ATC and PDTC [162]. The same combination is under study in DTC and PDTC naïve or progressing after lenvatinib patients (NCT02973997). Triple combined therapy (cabozantinib plus nivolumab and ipilimumab) is under evaluation for DTC and PDTC (NCT03914300).
