1156O - Surufatinib (S) for patients (Pts) with advanced pancreatic neuroendocrine tumours (SANET-p): A randomized, double-blind, placebo (P)-controlled phase III trial (NCT02589821)

Background

Surufatinib, a kinase inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptor 1 and colony stimulating factor-1 receptor, has demonstrated superior efficacy in extra-pancreatic neuroendocrine tumors (NETs) in a prior phase III study (ESMO 2019 Abs. LBA76). Here we report results from a parallel study of surufatinib in pancreatic NETs (pNETs).

Methods

The study evaluated the efficacy and safety of S in Pts with well-differentiated (pathological grade 1 or 2), progressive, unresectable or metastatic pNETs. Pts were randomized in a 2:1 ratio to receive S or P, 300 mg, orally, once daily, until disease progression or intolerable adverse events. Crossover at disease progression was allowed. The primary endpoint was investigator-assessed progression-free survival (PFS).

Results

By the cutoff date on 11 November 2019 for the pre-planned interim analysis, 172 Pts were randomized, 113 pts to S and 59 to P. Baseline characteristics were well balanced. The study met the primary endpoint; investigator-assessed median PFS was 10.9 vs. 3.7 months in S and P arms, respectively, with hazard ratio (HR)=0.491; 95% confidence interval [CI]: 0.319–0.755; p=0.0011. Analysis by a blinded independent radiology committee confirmed PFS improvement (13.9 vs. 4.6 months; HR=0.339; 95% CI: 0.209–0.549; p<0.0001). The investigator-assessed objective response rate was 19.2% with S and 1.9% with P (p=0.0021). Most common (≥5% in either arm) grade ≥3 treatment-emergent adverse events (TEAEs) were hypertension (38.9% in S arm vs. 8.5% in P arm), proteinuria (9.7% vs. 1.7%), hypertriglyceridaemia (7.1% vs. 0), alanine aminotransferase increased and gamma-glutamyltransferase increased (both 2.7% vs. 5.1%). TEAEs leading to drug discontinuation occurred in 10.6% pts vs. 6.8% pts in S and P arm respectively.

Conclusions

Surufatinib significantly improved the PFS in Pts with progressive, well-differentiated advanced pNETs. The safety profile was manageable and consistent with observations in prior studies. Surufatinib represents a promising treatment option in the armamentarium against pNETs.

Clinical trial identification

NCT02589821.

Editorial acknowledgement

Legal entity responsible for the study

Hutchison MediPharma Limited.

Funding

Hutchison MediPharma Limited.

Disclosure

J. Li, S. Fan: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.