Abstract 424: An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: A case report
Authors: Zhang Shiheng , Liu Yuntong , Luo Jiamin , Fang Yu , Ma Tonghui , Zhang Xiaoyan , Guan Wei 
Published: July 2021

Abstract
Introduction: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapid spreading cancers. None of the existing therapies is optimum and most ATC patients experience rapid recurrence. The median overall survival (OS) of ATC patients is about 5 months. Here, we report an ATC patient, who experienced rapid recurrence after operation, achieved OS of 9 months by applying a novel strategy of combining anti-angiogenic agent, anlotinib with immunotherapeutic drug, sintilimab.
Case presentation: The female ATC patient was 78 years old. On September 24, 2019, she had total thyroidectomy of the left lobe and isthmus due to a 4.7 cm × 4.2 cm lump in the left anterior cervical region. The mass was diagnosed as anaplastic thyroid cancer (pT3Nx). Immunohistochemistry and molecular testing analysis of the tumor showed the tumor proportion score of programmed death-ligand 1 &lt;1% (PD-L1-negative), tumor mutation burden of 1.88 mut/Mb (TMB-low), microsatellite stable, and mutations of BAI1, CDKN1A, EIF1AX, HRAS, IKBKB, and TP53. One month after the surgery, the tumor (3.3 cm × 1.5 cm) reappeared accompanied by metastases in right lung and sigmoid colon, which deemed her ineligible for another surgery. The patient rejected the use of chemo- or radio-therapy. Since no effective therapies were available, a novel combo strategy was used for this patient: anti-angiogenic agent anlotinib orally 12 mg per day and 2-week on/1-week off; and the immunotherapeutic agent, sintilimab, administrated with 200 mg once every 3 weeks. 2.5 months after the treatment, the recurrent tumor was reduced to 2.5 cm × 1.8 cm, and no lesions were found in the lung and colons. The patient continued to take sintilimab and anlotinib and the disease was under control. During treatment, no adverse reactions were observed. However, she died in May 2020 of abnormal thyroid function. Partial response (PR) and OS of 9 months were achieved.
Discussion: In this case, the novel anti-angiogenic drug anlotinib was chosen because it was proven to be safe and effective in treating multiple cancers without targeted mutations. Although the patient did not have positive indicators for immunotherapy (PD-L1 negative/TMB-low), we added sintilimab for the previous evidences of synergistic effect of anti-angiogenic drugs and immunotherapy in other cancers. Anti-angiogenic drug could increase the expression of immune cell markers including PD-L1; moreover, normalized tumor vasculature could increase the infiltration of immune cells. Here, our case provides supportive evidence for using this combination in the treatment of ATC patients.
Conclusion: This case showed relatively good prognosis after using anti-angiogenic agent, anlotinib, and immunotherapeutic drug, sintilimab, suggesting a new direction in treating recurrent and inoperable ATC patients, and also providing a new way for cancer patients with PD-L1 negative/TMB-low.
Citation Format: Shiheng Zhang, Yuntong Liu, Jiamin Luo, Yu Fang, Tonghui Ma, Xiaoyan Zhang, Wei Guan. An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: A case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 424.