Abstract
BackgroundSurufatinib (HMPL-012, previously named sulfatinib) is a small-molecule kinase inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptor 1 and colony stimulating factor 1 receptor, which demonstrated encouraging efficacy in previous Phase Ib/II study in patients with advanced NETs regardless of tumor origin. MethodsThis was a randomized, double-blind, multi-center phase III study to evaluate efficacy and safety of surufatinib in patients with well-differentiated, progressive, unresectable or metastatic extrapancreatic NETs (NCT02588170). Eligible patients were randomized in a 2:1 ratio to receive surufatinib or placebo, 300mg, orally, once daily, until disease progression or intolerable adverse events. Crossover at disease progression was allowed. The primary endpoint was disease progression-free survival (PFS) assessed by investigators. ResultsBy the cutoff date on 31 March 2019 for the pre-planned interim analysis, 198 patients were randomized (surufatinib: N=129, placebo N=69) with 128 PFS events observed. The tumor origins included gastrointestinal tract (47.0%), lung (11.6%), other (27.8%) or unknown (13.6%). Most patients (83.8%) were with NETs of pathological grade 2. Investigator-assessed median PFS was 9.2 vs. 3.8 months in surufatinib and placebo arms (hazard ratio [HR] = 0.334 [95% confidence interval [CI] 0.223, 0.499]; p<0.0001), respectively. A trend of PFS prolongation (HR=0.657, 95% CI 0.442, 0.977) was observed by the independent radiology committee. Overall survival (OS) was immature at data cutoff (18.7% OS events). Most common (≥5%) grade 3 or worse treatment-emergent adverse events were hypertension (36.4% in surufatinib arm vs. 13.2% in placebo arm), proteinuria (19.4% vs. 0%) and anemia (7.0% vs. 2.9%). ConclusionsSurufatinib significantly improved the PFS in patients with progressive, advanced NETs originating outside of pancreas. No new safety signals were identified. The study was terminated by the recommendation of the Independent Data Monitoring Committee based on the interim analysis. A parallel study of surufatinib in pancreatic NETs is ongoing. Legal entity responsible for the studyHutchison MediPharma Ltd. FundingHutchison MediPharma Ltd. DisclosureJ. Li: Full / Part-time employment: Hutchison MediPharma Ltd. S. Fan: Full / Part-time employment: Hutchison MediPharma Ltd. W. Su: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. All other authors have declared no conflicts of interest.
Published Version
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