As reported in The Lancet Oncology by Xu et al, the Chinese phase III SANET-p trial has shown significantly improved progression-free survival with surufatinib vs placebo in patients with advanced pancreatic neuroendocrine tumors. Surufatinib is a novel small-molecule inhibitor that targets VEGFR-1, VEGFR-2, VEGFR-3, FGFR1, and CSF-1R.
Study Details
The double-blind multicenter trial included 172 patients with well-differentiated pancreatic neuroendocrine tumors with disease progression on up to two previous systemic regimens for advanced disease. They were randomly assigned 2:1 between February 2016 and November 2019 to receive 300 mg of oral surufatinib (n = 113) or placebo (n = 59) once daily in consecutive 4-week cycles until disease progression, intolerable toxicity, poor compliance, or use of other antitumor medication. Crossover to surufatinib was permitted for patients in the placebo group with disease progression.
The primary endpoint was investigator-assessed progression-free survival in the intent-to-treat population. Overall, 65% of patients in the surufatinib group and 66% in the placebo group had received any kind of prior systemic therapy.
Progression-Free Survival
A preplanned interim analysis was performed at a median follow-up of 19.3 months in the surufatinib group and 11.1 months in the placebo group. Median progression-free survival was 10.9 months (95% confidence interval [CI] = 7.5–13.8 months) in the surufatinib group vs 3.7 months (95% CI = 2.8–5.6 months) in the placebo group (hazard ratio [HR] = 0.49, 95% CI = 0.32–0.76; P = .0011). The trial met the early stopping criteria at the interim analysis and was terminated on a recommendation from the independent data monitoring committee.
KEY POINTS
- Surufatinib significantly prolonged progression-free survival vs placebo.
- Median progression-free survival was 10.9 months vs 3.7 months.
On blinded independent review committee assessment, median progression-free survival was 13.9 months (95% CI = 11.0–24.9 months) in the surufatinib group vs 4.6 months (95% CI = 3.6–7.4 months) in the placebo group (HR = 0.34, 95% CI = 0.21–0.55, P < .0001).
A total of 31 (53%) of 59 patients in the placebo group crossed over to receive open-label surufatinib. Overall survival data were not mature at the time of interim analysis; at the time of analysis, death had occurred in 18% of patients in the surufatinib group and 15% of patients in the placebo group.
Adverse Events
The most common grade ≥ 3 treatment-related adverse events in the surufatinib group were hypertension (38% vs 7% of placebo group), proteinuria (10% vs 2%), and hypertriglyceridemia (7% vs 0%). Treatment-related serious adverse events were reported in 22% vs 7% of patients, with the most common in the surufatinib group being proteinuria in 4%, and ascites, diarrhea, gastrointestinal hemorrhage, vomiting, and liver injury in 2% each. Adverse events led to death in two patients in the surufatinib group, with causes consisting of gastrointestinal hemorrhage (considered possibly treatment-related) and cerebral hemorrhage.
The investigators concluded, “Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic neuroendocrine tumors, and could be a potential treatment option in this patient 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 thelancet.com.
