Results of a dose-escalation/expansion study in the US population among patients with extrapancreatic and pancreatic neuroendocrine tumors (NETs) indicate promising antitumor activity of the multitargeted tyrosine kinase inhibitor surufatinib, with a safety profile consistent with that previously described in the SANET-ep trial.
Surufatinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1, 2, and 3, FGFR1, and CSF1R that has demonstrated significant prolongation of progression-free survival (PFS) compared with placebo in a large phase 3 randomized study (SANET-ep trial; NCT02588170) in Chinese patients with advanced extrapancreatic NETs.1 Based on these promising results, a dose-escalation/expansion study (NCT02549937) was initiated to evaluate and confirm the efficacy and safety of surufatinib in the US population among patients with extrapancreatic and pancreatic NETs; the results of this ongoing study were presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.
The dose-escalation phase was completed and the maximum tolerated dose and recommended phase 2 dose was established as 300 mg daily, which was consistent with previous results. The primary objective of the dose-expansion phase of the study was to evaluate anticancer activity in patients with biliary tract tumors, soft-tissue sarcomas, pancreatic NETs, and extrapancreatic NETs. The primary end point was PFS; secondary end points included overall response rate (ORR), disease control rate (DCR), time to response, duration of response, safety, and pharmacokinetics.
At the time of analysis (April 2020), 32 patients with progressive NETs (pancreatic NETs, 16; extrapancreatic NETs, 16) were enrolled. These patients were heavily pretreated, with a median of 3 prior lines of treatment (range, 1-8) and had all previously received everolimus and/or sunitinib. Five patients with pancreatic NETs and 10 with extrapancreatic NETs remain on active treatment. The median duration of treatment was 19 weeks for all patients (30.9 weeks for pancreatic NETs and 11 weeks for extrapancreatic NETs). Nine patients discontinued because of disease progression, 2 withdrew consent, and 2 discontinued because of adverse events (AEs; grade 3 tricuspid valve insufficiency and grade 3 gastrointestinal bleed).
An ORR of 18.8% was achieved in patients with pancreatic NETs, including 3 partial responses; stable disease was achieved by 13 patients, for a DCR of 100%. There were responses achieved in the extrapancreatic NET cohort; all patients achieved disease stabilization for a 100% DCR. The median duration of treatment was 7.1 months (range, 2.0-17.5 months) in the pancreatic NET cohort and 4.9 months (range, 1.0-10.2 months) in the extrapancreatic NET cohort. Responses were achieved independent of prior lines of therapy.
The safety profile of surufatinib in the US trial was consistent with that previously described in Chinese patients.1 Of the 32 patients evaluable for safety evaluation, 30 (93.8%) patients experienced ≥1 AEs; of these, 22 (68.8%) patients reported grade ≥3 AEs. The most common grade 3/4 AEs included hypertension, diarrhea, proteinuria, and hematuria. Five patients discontinued treatment because of AEs.
These results demonstrate promising antitumor activity of surufatinib in the US population of patients with progressive NETs. The safety profile was consistent with previous reports, with no emergence of new safety signals.
Source: Dasari A, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4610.
Reference 1. Xu J, et al. ESMO 2019. Abstract LBA76.
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