Novel Small-Molecule Inhibitor Surufatinib for Advanced Extrapancreatic Neuroendocrine Tumors

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In the Chinese phase III SANET-ep trial reported in The Lancet Oncology, Xu et al found that surufatinib improved progression-free survival vs placebo in patients with advanced extrapancreatic neuroendocrine tumors. Surufatinib is a novel small-molecule inhibitor that targets VEGFR-1, VEGFR-2, VEGFR-3, FGFR1, and CSF-1R.

Study Details

In the double-blind multicenter study, 198 patients with well-differentiated disease and progression on no more than two types of previous systemic regimens were randomly assigned 2:1 between December 2015 and March 2019 to receive oral surufatinib at 300 mg per day (n = 129) or placebo (n = 69). Crossover to open-label surufatinib was permitted at disease progression in patients assigned to receive placebo. The primary endpoint was investigator-assessed progression-free survival in the intent-to-treat population. The current analysis was a preplanned interim analysis performed at 70% of predicted progression-free survival events.

Progression-Free Survival

Median follow-up was 13.8 months in the surufatinib group and 16.6 months in the placebo group. Median progression-free survival was 9.2 months (95% confidence interval [CI] = 7.4–11.1 months) in the surufatinib group vs 3.8 months (95% CI = 3.7–5.7 months) in the placebo group (hazard ratio [HR] = 0.33, 95% CI = 0.22–0.50, P < .0001). Since the trial met the predefined criteria for early discontinuation at the interim analysis, the study was terminated early on independent data monitoring committee recommendation. On blinded independent review committee assessment, median progression-free survival was 7.4 months vs 3.9 months (HR = 0.66, 95% CI = 0.44–0.98, P = .037).  

A total of 30 patients (43%) in the placebo group crossed over to receive open-label surufatinib. Overall survival data were not mature at the time of interim analysis. Death occurred in 27 (21%) of 129 patients in the surufatinib group and in 10 (14%) of 69 patients in the placebo group. Survival follow-up is ongoing.


  • Surufatinib significantly prolonged investigator-assessed progression-free survival vs placebo.
  • Median progression-free survival was 9.2 vs 3.8 months.

Adverse Events

The most common grade ≥ 3 treatment-related adverse events in the surufatinib group were hypertension (36% vs 13% in the placebo group), proteinuria (19% vs 0%), anemia (5% vs 3%), increased aspartate aminotransferase (5% vs 3%), increased blood pressure (4% vs 3%), protein present in urine (4% vs 0%), hyperbilirubinemia (4% vs 0%), and increased alanine aminotransferase (3% vs 0%). Treatment-related serious adverse events were reported in 25% vs 13% of patients, with the most common in the surufatinib group (all 2%) being cholestatic jaundice, abdominal pain, gastrointestinal hemorrhage, intestinal obstruction, and anemia. Treatment-related deaths occurred in three patients in the surufatinib group (due to disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown cause) and one patient in the placebo group (due to cachexia and respiratory failure).

The investigators concluded, “Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favorable benefit-to-risk profile in patients with progressive, advanced, well-differentiated extrapancreatic neuroendocrine tumors. Our results suggest that surufatinib might be a new treatment option for this population.”

Jianming Xu, MD, of the Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Hutchison MediPharma. For full disclosures of the study authors, visit

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