Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies

ESMO Open

article

J. Li¹  Y. Cheng¹  C. Bai¹  J. Xu²  L. Shen³  J. Li³  Z. Zhou⁴  Z. Li⁵  Y. Chi⁶  X. Yu⁷  E. Li⁸  N. Xu⁹  T. Liu^1,10  W. Lou^1,10  Y. Bai^1,11  X. Yuan^1,12  X. Wang^1,13  Y. Yuan^1,14  J. Chen^1,15  S. Guan^1,16  S. Fan^1,16  W. Su^1,16 

[1] Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital;Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research ,(Ministry of Education), Peking University Cancer Hospital & Institute;Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center;Department of Abdominal Oncology, West China Hospital, Sichuan University;National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center;Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University;Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University;Department of General Surgery, Zhongshan Hospital of Fudan University;Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital;Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Medical Oncology, Qilu Hospital of Shandong University;Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine;Department of Oncology, Jiangsu Cancer Hospital;Department of Clinical and Regulatory Affairs

关键词: neuroendocrine tumor;    surufatinib;    SANET;    biomarker;    adverse event;   

DOI  :  10.1016/j.esmoop.2022.100453

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background No validated biomarkers currently exist for predicting the efficacy outcomes in patients with neuroendocrine tumors (NETs) treated with antiangiogenic therapy. We aimed to evaluate the association between treatment-related adverse events (TRAEs) and efficacy outcomes of surufatinib in patients with advanced NET.Patients and methods We included patients with NET treated with surufatinib in two multicenter, randomized, double-blind, placebo-controlled, phase III trials (SANET-p and SANET-ep) in this study. The main exposure was the presence of any of the TRAEs including hypertension, proteinuria, and hemorrhage in the first 4 weeks of surufatinib treatment. The primary outcome of the study was investigator-assessed progression-free survival (PFS). PFS outcomes were estimated using the Kaplan–Meier method with the log-rank test. Hazard ratios (HRs) were calculated by using univariable and multivariable Cox proportional hazard regression models. Blinded independent image review committee (BIIRC) assessments and 4-week landmark analysis were also performed as supportive evaluations.Results During the study period, a total of 242 patients treated with surufatinib were included in the analysis, and 164 (68%) patients had at least one of hypertension, proteinuria, and hemorrhage in the first 4 weeks of treatment. The presence of TRAEs in the first 4 weeks was associated with prolonged median PFS [11.1 versus 9.2 months; HR 0.67, 95% confidence interval (CI) 0.47-0.97; P = 0.036]. In multivariable Cox regression analysis, the presence of TRAEs was also significantly associated with longer PFS (HR 0.65, 95% CI 0.44-0.97; P = 0.035). Similar results were obtained in the BIIRC assessments and 4-week landmark analysis.Conclusions Treatment-related hypertension, proteinuria, and hemorrhage could be potential biomarkers to predict antitumor efficacy of surufatinib in patients with advanced NET. Future prospective studies are needed to validate the findings.

【 授权许可】

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