Endocrine Abstracts

Background: Surufatinib targets VEGFR1-3, FGFR1 and CSF1R, is a novel oral tyrosine kinase inhibitor (TKI) with dual antiangiogenic and immunomodulatory activities. It has been approved for the treatment of well-differentiated neuroendocrine tumors. Octreotide LAR, a somatostatin analogue, has been approved for the treatment of G1/G2 GEP-NET. This study aims is to investigate the efficacy and safety of surufatinib combined with octreotide LAR in the treatment of G1/G2 GEP-NET.

Methods: This single-arm, prospective, open-label phase II clinical study included patients aged 18-75 years with unresectable locally advanced or distant metastasis G1/G2 GEP-NET, ECOG PS 0-1, and adequate organ and bone marrow function. Patients received surufatinib (300 mg, po, qd) and octreotide LAR (30 mg, sc, q4w) until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.

Results: As of August 5, 2024, 8 patients were enrolled, and 7 were assessable, with a median age of 59 years (range 40-66), and 57.1% females. Most were G2 (71.4%) with a median Ki-67 index of 5% (range: 2-10%). The primary sites included rectum (42.9%), pancreas (28.6%), gastric (14.3) and small intestine (14.3%). All of them had liver metastases. 28.6% had prior anti-tumor therapy. With 15.7 months median follow-up, the 6-month and 12-month PFS rates were 100.0% and 66.7% (95%Cl 37.9-100.0%). 2 patients progressed, 5 remain on treatment, 4 beyond 14 months (24.6, 20.1, 14.9, 14.2 months). The ORR and DCR were 28.6% and 100.0%, respectively. The most common treatment-related adverse events (TRAEs) were proteinuria (62.5%), lactate dehydrogenase increased (37.5%) and thyroid stimulating hormone increased (37.5%). Grade 3 TRAEs were proteinuria (12.5%) and hypertension (12.5%). No grade 4 TRAEs or deaths were reported.

Conclusions: This first study demonstrates promising antitumor activity and manageable safety of surufatinib plus octreotide LAR in G1/2 GEP-NET patients. The results support further evaluation of the therapy in a larger population. This trial is ongoing and updated data will be presented in the future.

ABSTRACT ID28484