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科学出版物 | 2022-06-06

ASCO2022: 两项 Ⅲ 期临床试验中索凡替尼治疗晚期 NETs 患者的安全性汇总分析

A pooled analysis of surufatinib safety from phase 3 trials in advanced NETs

 

Authors

Jie Li, Jianming Xu, Lin Shen, Chunmei Bai, Zhiwei Zhou, Zhiping Li, Yihebali Chi, Xianjun Yu, Enxiao LI, Nong Xu, Tianshu Liu, Wenhui Lou, Yuxian Bai, Xianglin Yuan, Xiuwen Wang, Ying Yuan, Jia Chen, Tao Zhang, Dianrong Xiu, Weiguo Su

Organizations:

Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China, Department of Oncology, Peking Union Medical College Hospital, Beijing, China, Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xian, China, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China, Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China, Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Department of Medical oncology, Qilu Hospital of Shandong University, Jinan, China, Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, Department of Oncology, Jiangsu Cancer Hospital, Nanjing, China, Cancer Centre, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Department of General Surgery, Peking University Third Hospital, Beijing, China, HUTCHMED Limited, Shanghai, China

 

Background:

Surufatinib is a small-molecule inhibitor of VEGFR1, 2, & 3, FGFR1, and CSF-1R. Surufatinib demonstrated prolonged PFS and tolerable safety in two phase 3 studies in advanced neuroendocrine tumors (NETs) of pancreatic (SANET-p; NCT02589821) and extrapancreatic (SANET-ep; NCT02588170) origin (Xu, 2020 Lancet Oncology). Detailed outcomes on safety from these 2 studies are reported here as a pooled analysis.

 

Methods:

Data is pooled from SANET-p and SANET-ep studies which have similar designs including a 2:1 randomization of surufatinib to placebo in patients ≥18 years with advanced, well differentiated NETs, progressing on or after ≤2 prior therapies. Surufatinib 300 mg or placebo, was administered once daily until disease progression or unacceptable toxicity. Safety outcomes for each pooled treatment group are reported as treatment-emergent adverse events (TEAE) assessed by NCI-CTC 4.03. Patients were included if they had received study treatment during the double-blinded phase of the studies.

 

Results:

As of 30th June 2020, 396 patients were assigned to the surufatinib (n = 263) and placebo (n = 133) groups. Median treatment duration was longer with surufatinib 7.4 months (range 0.1–41.4) compared with placebo 4.6 months (range 0.1–39.9). 29% of patients reached more than 12 months of treatment with surufatinib group compared to 11% with placebo. The mean relative dose intensity was 87.56% in the surufatinib group and 97.01% in the placebo group. Most common TEAEs (surufatinib vs placebo) were proteinuria 68.8% vs 54.9%, hypertension 68.4% vs 27.1%, and diarrhea 49% vs 22.6%. Most common grade ≥3 TEAE were hypertension 38.8% vs 13.5%, proteinuria 14.8% vs 0.8% and hypertriglyceridaemia 5.3% vs 0%. Deaths due to TEAEs were comparable between groups 2.7% vs 2.3%. TEAEs led to dose reductions in 43.0% vs 6.8% of patients and dose interruptions in 47.1% vs 29.3% of patients. The majority of patients (83.3% vs 93.2%) were managed without discontinuation because of TEAE. Median onset of proteinuria and hypertension were < 1 month in both groups. Median (range) onset was 0.95 months (0.16–30.36) vs 0.95 months (0.23–16.95) for proteinuria and 0.49 months (0.03–31.18) vs 0.89 months (0.03–14.75) for hypertension. Among patients with hypertension, 59% (n = 111) vs 28% (n = 11) received antihypertensive medication.

 

Conclusions:

Surufatinib was generally well tolerated in this pooled analysis and the safety profile was consistent with its previously reported data. The monitoring and management of hypertension and proteinuria are important for patients receiving surufatinib. Clinical trial information: NCT02589821; NCT02588170.

Most frequent TEAEs (PT≥30%), % S
(N = 263)
P
(N = 133)
Any Gr.≥3 Any Gr. ≥3
Proteinuria 68.8 14.8 54.9 0.8
Hypertension 68.4 38.8 27.1 13.5
Diarrhea 49.0 2.3 22.6 0.8
Blood thyroid stimulating hormone increased 42.6 0 9.8 0
Blood bilirubin increased 37.6 1.9 19.5 0
Hypertriglyceridemia 35.7 5.3 12.0 0
Occult blood positive 33.1 0 21.8 0
AST increased 30.8 3 30.8 3