Introduction: Anaplastic thyroid carcinomas (ATC) and metastasized PDTC have a dismal prognosis of only few months despite extensive multimodal therapy. The tumors are high-proliferative and aquire numerous somatic mutations (often over several hundred mutations). These specifics implicate a special sensitivity of the tumors towards anti-angiogenic therapies and immune checkpoint inhibitors.
In the presented cases, we have combined anti-angiogenic therapy with lenvatinib and the immune checkpoint inhibitor pembrolizumab in 8 patients with metastasized ATC (n = 6) or metastasized PDTC (n = 2). All patient tumors had more than 100 somatic mutations as identified by whole exome sequencing (WES) and PD-L1 > 1%. Lenvatinib was started at 24 mg/kg BW and reduced to minimally 14 mg/kg BW upon appearance of intolerable side effects (uncontrollably high blood pressure, weight loss, loss of appetite). Pembrolizumab was started 3 - 8 weeks later and was given at a fixed dose of 200 mg every 3 weeks. Maximum treatment duration with this combination was 27 months (27, 24, 19, 11, 7, 6, 3, 1 month) and 6 patients are still on therapy.
No continuous °III/IV toxicities were seen with the combination treatment. Weight loss (3 pts) and uncontrollably high blood pressure (3 pts) were normalized after reducing lenvatinib doses. One patient died 5 days after the first dose of pembrolizumab due to disease progression of the cervical tumor. All other patients have reached at least a SD (n = 2), most patients had reached a PR (n = 4) and one patient has reached a complete remission (CR). The majority of patients is still on therapy (27,24,19,7,6 and 3 months), implicating this treatment combination as a safe and effective treatment regimen for this extremely bad prognostic patient cohort.
Our results implicate that a combination of lenvatinib and pembrolizumab is safe and effective in patients with ATC or PDTC. The combination treatment shall now be systematically examined in a phase II clinical trial (ATLEP) in ATC/PDTC patients.
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