👉Dierks C et al. 2021 The lenvatinib/pembrolizumab combination is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma. Thyroid. Epub 2021 Jan 28. PMID: 33509020.
👉Combination pembrolizumab plus lenvatinib may be a treatment option for patients with anaplastic and poorly differentiated thyroid cancer
BACKGROUND
👉Most types of thyroid cancer have an excellent prognosis and patients do well. Two significant exceptions are anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), both of which are rare but very aggressive types of thyroid cancer. Overall, ATC has an extremely high death rate and a 10-year survival of less than 5%. PDTC has a more favorable prognosis than ATC, however, the 10-year survival is still lower than 10%. One of the reasons for this poor prognosis is that neither of these thyroid cancers take up radioactive iodine, which serves as a magic bullet to kill thyroid cancer cells in the more common types of papillary and follicular thyroid cancer. Thus, treatment for ATC and PDTC is limited to surgery, with chemotherapy the only option if the cancer is persistent or recurrent after surgery.
👉Despite of the significant progress and the availability of numerous combination chemotherapies to treat cancer, treatment options for ATC and PDTC are still limited. The goal of this study was to evaluate the response of a combination of two new types of chemotherapy: a multikinase inhibitor (lenvatinib) and an immune checkpoint inhibitor (pembrolizumab) in patients with metastatic ATC and PDTC who failed standard chemotherapy
SUMMARY OF THE STUDY
👉This is a study of patients with metastatic ATC (6 patients) and PDTC (2 patients), who failed other treatments and received a combination therapy of lenvatinib and pembrolizumab between March 2016 and December 2019 at a medical center in Germany.
👉The patients were started on lenvatinib 20 to 24 mg daily and then pembrolizumab was added at a fixed dose of 200 mg intravenously every 3 weeks. The lenvatinib dose was progressively decreased if side effects occurred. Lenvatinib was given for at least 1 year and then stopped in patients with complete response to treatment after a maximum of 24 months. Pembrolizumab was continued after reaching a complete response for a maximum of 40 months during the study. The individual treatment duration was 1, 4, 11, 15, 19, 25, 27, and 40 months.
👉Based on the RECIST criteria, within 16 months of treatment, 4 out of 6 (66%) ATC patients had a complete remission, 1 (16%) had stable disease, and 1 (16%) had progressive disease and died within the first month of treatment. Both patients with PDTC had partial remission. The average time without disease progression was 17.75 months for all patients and 16.5 months for the ATC patients. The average survival time was 18.5 months, with 3 ATC patients being still alive without relapse (at 40, 27, and 19 months) despite metastatic disease at the start of treatment.
👉Most side effects resolved after decreasing the lenvatinib dose. However, this medication had to be discontinued in two patients due to severe weight loss/loss of appetite, while a patient had a severe bleeding leading to death while being in complete remission.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
👉The study results suggest that the combination therapy with lenvatinib and pembrolizumab is well tolerated in general and it might be an effective treatment in patients with ATC or PDTC, resulting in complete and long-term remissions. At present this combination treatment is being evaluated in patients with ATC and PDTC in a phase two clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab – ATLEP).
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Rodrigo Arrangoiz MS, MD, FACS, FSSO 