Surufatinib Induces Robust Responses in US Patients with Extrapancreatic and Pancreatic NETs


Surufatinib demonstrated strong antitumor activity along with a manageable safety profile in heavily treated US patients with progressive extrapancreatic neuroendocrine tumors or pancreatic NETs, according to interim phase 1 data.

Surufatinib demonstrated strong antitumor activity along with a manageable safety profile in heavily treated US patients with progressive extrapancreatic neuroendocrine tumors (ep-NETs) or pancreatic NETs (pNETs), according to interim phase 1 data presented in a poster at the 2021 NANETS Annual Meeting.1

In the findings presented at NANETS, investigators evaluated 16 patients with epNETs and 16 with pNETs in a dose-escalation and -expansion trial to evaluate the safety and efficacy of surufatinib in a US population. Results of the dose-expansion phase showed that the objective response rate was 6.3% (95% CI, 0.2%-30.2) in the epNET cohort and 18.8% (95% CI, 4.0%-45.6%) in the pNET group; all responses in both groups were partial responses. The disease control rates were, respectively, 93.8% (95% CI, 69.8%-99.8%) and 87.5% (95% CI, 61.7%-98.4%).

The 11-month progression-free survival (PFS) rate was 51.1% (95% CI, 12.8%-80.3%) in the epNETs cohort and 57.4% (95% CI, 28.7%-78.2%) in the pNETs cohort. The median PFS was 11.5 months (95% CI, 6.47-11.50) in the epNET group and 15.2 months (95% CI, 5.19–not reached) in the pNET group.

In the phase 1, dose-escalation/-expansion trial, the recommended phase 2 dose was set at 300 mg of daily surufatinib in the dose-escalation phase, which was the same dose established in phase 3 trials conducted in China. In the US trial, patients in the epNET cohort received a median of 8 cycles (range, 2-15) of treatment while the median was 8.5 (range, 2-23) in the pNET cohort. Seven patients remained on treatment at the June 2020 data cutoff.

The primary end point was investigator-assessed PFS rate at 11 months. Secondary end points included safety and pharmacokinetics.

Regarding patient characteristics, the median age was 63.3 years and 68.8% of patients in both cohorts were male. The baseline ECOG performance status was 0 or 1 for all patients. Those in the epNET arm received a median of 2 prior lines of therapy (range, 2-5) compared with 4 (range, 1-8) in the pNET arm. Thirty-two patients with heavily pretreated progressive NETs were enrolled in the dose-expansion phase. Seven patients remained on treatment (4 with epNETs and 3 with pNETs) remained on treatment at the June 30, 2020 data cutoff date. The median number of cycles received was 8 (range, 2-15) and 8.5 (range, 2-23) for the epNETs and pNETs groups, respectively.

Safety results were consistent with earlier findings from the phase 3 Chinese SANET-p (NCT02589821) and SANET-ep (NCT02588170) trials, in which investigators evaluated surufatinib in the pNET and epNET populations, respectively.

In the data presented at the 2021 NANETS Annual Meeting, the most common grade 3 or higher treatment-emergent adverse events (TEAEs) were hypertension (37.5%) and diarrhea (12.5%) in the epNET group and hypertension (37.5%) in the pNET group.

Serious AEs were observed in 43.8% of patients. Seven (21.9%) patients required treatment discontinuation due to AEs. Nine (28.1%) needed dose reductions and 18 (56.3%) needed dose interruptions due to TEAEs.

Based on the SANET-p data, the National Medical Products Administration of China approved surufatinib in June 2021 for the treatment of patients with advanced pNETs. Additionally, the FDA accepted the filing of a new drug application for surufatinib as a potential treatment option for patients with pNETS and epNETS.2 The agency slated to decide on the application by April 30, 2022, under the Prescription Drug User Fee Act.

In SANET-p, 172 adult patients with progressive, advanced, well-differentiated pNETs were randomly assigned to daily oral surufatinib at 300 mg (n = 113) or placebo (n = 59) in 4-week treatment cycles.3

The median PFS per investigator assessment was 10.9 months (95% CI, 7.5-13.8) with surufatinib vs 3.7 months (95% CI, 2.8-5.6) with placebo (HR, 0.49; 95% CI, 0.32-0.76; P = .0011). An independent data monitoring committee recommended termination of the trial, as it met the early stopping criteria at the interim analysis.

The safety data showed that the most frequent grade 3 or higher treatment-related adverse effects (TRAEs) included hypertension (38% vs 7%), proteinuria (10% vs 2%), and hypertriglyceridemia (7% vs 0%). Serious TRAEs occurred in 22% and 7% of those in the investigative and control arms, respectively. Three on-treatment deaths occurred on the surufatinib arm vs 1 on the placebo arm.

In SANET-ep, 198 patients with unresectable or metastatic, well differentiated, epNETs were assigned to the same schedule of surufatinib (n = 129) or matching placebo (n = 69) in a 2:1 randomization.4

Here, the investigator-assessed median PFS was 9.2 months (95% CI, 7.4-11.1) vs 3.8 months (95% CI, 3.7-5.7) with placebo (HR, 0.33; 95% CI, 0.22-0.50; P <.0001). Similarly, an independent data monitoring committee again recommended termination because the study met the early stopping criteria.

Regarding safety, the most common grade 3 or higher in patients who received surufatinib or placebo included hypertension (36% vs 13%) and proteinuria (19% vs 0%). Twenty-five percent of patients in the investigation arm experienced serious TRAEs compared with 13% for those in the control arms. Three patients who received surufatinib died, which were related to treatment compared with 1 who received placebo.


  1. Li D, Paulson S, Tucci C, et al. Interim analysis results of surufatinib in US patients with neuroendocrine tumors (NETs). Presented at: 2021 NANETS Annual Meeting; November 3-6, 2021; virtual. Abstract 105.
  2. US FDA accepts filing of HUTCHMED’s NDA for surufatinib for the treatment of advanced neuroendocrine tumors. News release. July 1, 2021. Accessed July 1, 2021.
  3. Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(11):1489-1499. doi:10.1016/S1470-2045(20)30493-9
  4. Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(11):1500-1512. doi:10.1016/S1470-2045(20)30496-4
Related Videos
Riccardo Lencioni, MD, FSIR, EBIR
Tycel Phillips, MD
Ajai Chari, MD
Manish A. Shah, MD
Alexey Danilov, MD, PhD
Hayder Saeed, MD
Jeremy L. Ramdial, MD, assistant professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Alexandra Gomez Arteaga, MD, Weill Cornell Medicine/New York-Presbyterian Hospital
Rahul Banerjee, MD, FACP, assistant professor, Clinical Research Division, Fred Hutchinson Cancer Center; assistant professor, Division of Hematology and Oncology, University of Washington
Alice Bertaina, MD, PhD