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THYROID CANCER
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 patient do well. Two significant exceptions are anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), both of which are rare but very aggressive type 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 2 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.
THE FULL ARTICLE TITLE
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.
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 2 clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab – ATLEP).
—Alina Gavrila, MD, MMSc
ATA THYROID BROCHURE LINKS
Anaplastic Thyroid Cancer – https://www.thyroid.org/anaplastic-thyroid-cancer/
Thyroid Cancer (Papillary and Follicular): https://www.thyroid.org/thyroid-cancer/
ABBREVIATIONS & DEFINITIONS
Metastatic Cancer: spread of the cancer from the initial organ where it developed to other organs, such as the lungs and bone.
Cancer remission: disappearance or decrease in severity of the signs and symptoms of cancer.
Radioactive iodine (RAI): this plays a valuable role in diagnosing and treating thyroid problems since it is taken up only by the thyroid gland. I-131 is the destructive form used to destroy thyroid tissue in the treatment of thyroid cancer.
Multikinase inhibitors: cancer medications that decrease the tumor growth and spread by blocking multiple enzymes (kinases) located at the surface or inside the cancer cells. Kinases are overactive in many of the pathways that cause cells to be cancerous.
Immune checkpoint inhibitors: cancer medications that block immune checkpoint proteins, thus allowing the immune cells in the body to kill cancer cells. As part of the immune system, checkpoint proteins prevent an immune response from being too strong and destroying healthy cells in the body;
RECIST (Response Evaluation Criteria in Solid Tumors): this is a set of published rules that define when cancer patients improve (“respond”), stay the same (“stable”) or worsen (“progression”) during treatments.
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