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Surufatinib in Advanced Well-Differentiated Neuroendocrine Tumors: A Multicenter, Single-Arm, Open-Label, Phase Ib/II Trial

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机构: [1]Department of Gastrointestinal Oncology, The Fifth Medical Center, GeneralHospital of People's Liberation Army, Beijing, China [2]Department of GastrointestinalOncology, Key laboratory of carcinogenesis and Translational Research(Ministry of Education), Peking University Cancer Hospital & Institute, Beijing,China [3]Department of Oncology, Peking Union Medical College Hospital, Beijing,China [4]Department of Medical Oncology, The First Affiliated Hospital of ZhejiangUniversity, Hangzhou, China [5]Department of Gastric and PancreaticSurgery, Sun Yat-sen University Cancer Center, Guangzhou, China [6]Departmentof Abdominal Oncology, West China Hospital, Sichuan University, Chengdu,China [7]Department of Oncology, Shanghai Pulmonary Hospital, School ofMedicine, Tongji University, Shanghai, China [8]Hutchison MediPharma Limited,Shanghai, China [9]School of Mathematical Sciences, Shanghai Jiao Tong University,Shanghai, China
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Purpose: No antiangiogenic treatment is yet approved for extrapancreatic neuroendocrine tumors (NET). Surufatinib (HMPL-012, previously named sulfatinib) is a small-molecule inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptor 1 and colony-stimulating factor 1 receptor. We conducted a single-arm phase Ib/II study of surufatinib in advanced NETs. Patients and Methods: Patients with histologically well-differentiated, low or intermittent grade, inoperable or metastatic NETs were enrolled into a pancreatic or extrapancreatic NET cohort. Patients were treated with surufatinib 300 mg orally, once daily. The primary endpoints were safety and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (version 1.1). Results: Of the 81 patients enrolled, 42 had pancreatic NETs and 39 had extrapancreatic NETs. Most patients had radiologic progression within 1 year prior to enrollment (32 patients in each cohort). In the pancreatic and extrapancreatic NET cohorts, ORRs were 19% [95% confidence intervals (CI), 9-34] and 15% (95% CI, 6-31), disease control rates were 91% (95% CI, 77-97) and 92% (95% CI, 79-98), and median progression-free survival was 21.2 months (95% CI, 15.9-24.8) and 13.4 months (95% CI, 7.6-19.3), respectively. The most common grade >= 3 treatment-related adverse events were hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia, and diarrhea (6% for each), and increased alanine aminotransferase (5%). Conclusions: Surufatinib showed encouraging antitumor activity and manageable toxicities in patients with advanced NETs. Two ongoing phase III studies, validating the efficacy of surufatinib in patients with NETs, will contribute to the clinical evidence.

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出版当年[2019]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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出版当年[2019]版:
Q1 ONCOLOGY
最新[2023]版:
Q1 ONCOLOGY

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第一作者机构: [1]Department of Gastrointestinal Oncology, The Fifth Medical Center, GeneralHospital of People's Liberation Army, Beijing, China [*1]The Fifth Medical Center, General Hospital of People's Liberation Army Beijing 100071, China
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通讯机构: [1]Department of Gastrointestinal Oncology, The Fifth Medical Center, GeneralHospital of People's Liberation Army, Beijing, China [*1]The Fifth Medical Center, General Hospital of People's Liberation Army Beijing 100071, China
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