Surufatinib improved progression-free survival compared with placebo in patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumors for whom there is no effective therapy.
Surufatinib improved progression-free survival (PFS) compared with placebo in patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumors (pNETs) for whom there is no effective therapy, according to a preplanned interim analysis of the phase III SANET-p trial (NCT02589821) that was completed by an independent data monitoring committee (IDMC).1
As a result, the IDMC recommended that the study be stopped early, as the predefined primary endpoint, which is PFS, was met. Chi-Med, the developer of surufatinib, stated in a press release that it plans to meet with the China National Medical Products Administration (NMPA) to discuss preparing a new drug application (NDA) for the agent in this indication. Full findings of the trial will be presented at an upcoming medical meeting.
“This positive data is a further important milestone for Chi-Med,” Christian Hogg, chief executive officer of Chi-Med, stated in a press release. “Following surufatinib’s NDA submission for the treatment of non-pancreatic neuroendocrine tumors, these positive results for pancreatic neuroendocrine tumors reinforce that surufatinib has the unique opportunity to address all advanced neuroendocrine tumors. We believe that no targeted therapies are approved in China or globally for such a broad spectrum of neuroendocrine tumor disease.”
In November 2019, the FDA granted an orphan drug designation to surufatinib for the treatment of patients with pNETs. Additionally, Chi-Med stated that a China new drug application for surufatinib as a treatment for patients with advanced non-pNETs was accepted for review by the NMPA, and was subsequently granted a priority review designation in December 2019.
In the phase III SANET-p study, approximately 195 Chinese patients with low- or intermediate-grade advanced pNETs for whom there is no effective therapy were randomized 2:1 to receive either 300 mg of oral surufatinib daily or placebo on a 28-day cycle.
To be eligible for enrollment, patients had to be ≥18 years old, had previously progressed on ≤2 types of systemic therapy, had radiological documentation of disease progression within 12 months prior to randomization, had measurable lesions according to RECIST v1.1 criteria, had an ECOG performance status of 0 or 1, an expected survival of ≥12 weeks, and an absolute neutrophil count of ≥1.5 x 109/L, platelet count of ≥100 x 109/L, and hemoglobin of ≥9 g/dL, among other criteria.
Patients who have high-grade neuroendocrine cancer, adenocarcinoid, pancreatic islet cell carcinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma were excluded from enrollment. Additionally, patients could not have functional NETs that required treatment with long-acting somatostatin analogs to control disease-related syndromes, nor could they receive prior treatment with and had disease progression on a VEGF inhibitor.
The primary endpoint of the study is PFS; secondary endpoints include objective response rate (ORR), disease control rate, time to response, duration of response, overall survival, safety, and tolerability.
Previously, a multicenter, single-arm, open-label, phase Ib/II trial evaluated surufatinib in patients with histologically well-differentiated, low- or intermittent-grade, inoperable or metastatic NETs. Patients were stratified by pancreatic (n = 42) or extrapancreatic subtype (n = 39).
Results showed that the ORRs were 19% (95% CI, 9%-34%) in the pancreatic NETs cohort and 15% (95% CI, 6%-31%) in the extrapancreatic NET cohort.2 The median PFS was 21.2 months (95% CI, 15.9-24.8) and 13.4 months (95% CI, 7.6-19.3), respectively. Regarding safety, the most common grade ≥3 treatment-related adverse events included hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia (6%), diarrhea (6%), and increased alanine aminotransferase (5%).