Efficacy and safety of pralsetinib in Chinese advanced RET-mutant medullary thyroid cancer patients

in Endocrine-Related Cancer
Authors:
Xiangqian Zheng Thyroid Neck Oncology Department, Tianjin Medical University Cancer Institute & Hospital, Tianjin, Tianjin, China

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Meiyu Fang Department of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

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https://orcid.org/0000-0001-5791-1444
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Yun Fan Department of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

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Yuping Sun Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China

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Meili Sun Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China

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Ankui Yang Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

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Bin Zhang Head and Neck Surgery Department, Beijing Cancer Hospital, Beijing, Beijing, China

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Qinjiang Liu Head and Neck Surgery, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China

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Hui Liu Head and Neck Oncology Surgical Department, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China

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Xiaohong Zhou Head and Neck Surgery, Chongqing Cancer Hospital, Chongqing, Chongqing, China

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Tao Huang Breast and Thyroid Surgery, Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China

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Jianwu Qin Head and Neck Surgery, Henan Cancer Hospital, Zhengzhou, Henan, China

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Zhaohui Wang Head and Neck Surgery Department, Sichuan Cancer Hospital & Institute, Chengdu, Sichuan, China

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Mengmeng Qin Clinical Department, CStone Pharmaceuticals (Suzhou) Co., Ltd., Suzhou, Jiangsu, China

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Zhenwei Shen Clinical Department, CStone Pharmaceuticals (Suzhou) Co., Ltd., Suzhou, Jiangsu, China

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Sheng Yao Clinical Department, CStone Pharmaceuticals (Suzhou) Co., Ltd., Suzhou, Jiangsu, China

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Jason Yang Clinical Department, CStone Pharmaceuticals (Suzhou) Co., Ltd., Suzhou, Jiangsu, China

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Yu Wang Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, Shanghai, China

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Ming Gao Thyroid Neck Oncology Department, Tianjin Medical University Cancer Institute & Hospital, Tianjin, Tianjin, China
Department of Breast and Thyroid Surgery, Tianjin Union Medical Center, Tianjin, Tianjin, China

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https://orcid.org/0000-0002-0118-541X

Correspondence should be addressed to Y Wang or M Gao: neck130@hotmail.com or gaoming68@aliyun.com
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Pralsetinib has demonstrated efficacious activity in various solid tumors, including medullary thyroid cancer (MTC), as observed in the phase 1/2 global ARROW study (BLU-667-1101; NCT03037385). We evaluated the safety and efficacy of pralsetinib in Chinese patients with advanced RET-mutant MTC. In the extension cohort of ARROW, adult patients with advanced MTC, who had not received systemic therapy (except for cytotoxic chemotherapy), were treated with pralsetinib (400 mg once daily, orally). The primary endpoints were blinded independent central-reviewed (BICR) objective response rate (ORR) and safety. Between October 9, 2019, and April 29, 2020, 34 patients were enrolled at 12 centers across China. Among them, 28 patients tested positive for RET mutations in the central laboratory, and 26 of these, with measurable disease at baseline per BICR, were included in the analysis set for tumor response. As of April 12, 2021 (data cutoff), the ORR was 73.1% (95% CI: 52.2–88.4), and the median duration of response was not reached. The most common (≥15%) grade ≥3 treatment-related adverse events (TRAEs) in the 28 patients with RET-mutant MTC were neutrophil count decreased (8/28, 28.6%), blood creatine phosphokinase increased (6/28, 21.4%), and lymphocyte count decreased (5/28, 17.9%). Serious TRAEs were reported by six patients (21.4%), with the most common event being pneumonia (3/28, 10.7%). No patient discontinued treatment or died from pralsetinib-related adverse events. Pralsetinib demonstrated broad, deep, and durable efficacy, as well as a manageable and acceptable safety profile in Chinese patients with advanced RET-mutant MTC.

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