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

Abstract

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.

• Authors: Jianming Xu, Jie Li, Chunmei Bai, Nong Xu, Zhiwei Zhou, Zhiping Li, Caicun Zhou, Ru Jia, Ming Lu, Yuejuan Cheng, Chenyu Mao, Wei Wang, Ke Cheng, Chunxia Su, Ye Hua, Chuan Qi, Jing Li, Wei Wang, Ke Li, Qiaoling Sun, Yongxin Ren, Weiguo Su
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 25 Issue 12 Pg. 3486-3494 (06 15 2019) ISSN: 1557-3265 [Electronic] United States
• PMID: 30833272 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Protein Kinase Inhibitors
• Small Molecule Libraries
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Adult
• Aged
• Cell Differentiation (physiology)
• Cohort Studies
• Female
• Gastrointestinal Neoplasms (drug therapy, metabolism, pathology)
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Neuroendocrine Tumors (drug therapy, metabolism, pathology)
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Protein Kinase Inhibitors (adverse effects, pharmacokinetics, therapeutic use)
• Small Molecule Libraries (adverse effects, pharmacokinetics, therapeutic use)
• Survival Rate
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)
• Young Adult