Authors: J.M. Xu, J. Li, C.M. Bai, N. Xu, Z.W. Zhou, Z.P. Li, C.C. Zhou, W. Wang, J. Li, C. Qi, Y. Hua, W.G. Su
Summary: The current Phase Ib/II trial is an open-label, single-arm Phase II study to assess the efficacy and safety of sulfatinib monotherapy in patients with advanced grade 1 or 2 advanced NET. 81 patients (41 pancreatic NET and 40 extra-pancreatic NET) were enrolled between November 2014 and January 2016, in seven clinical centers across China. The majority of patients had grade 2 disease (79%) and had failed previous systemic treatments (65%). As of January 20, 2017, 13 patients had confirmed partial response (“PR”) and 61 patients had stable disease (“SD”) corresponding to an overall objective response rate (“ORR”) of 16.0% (13/81), with 17.1% (7/41) in pancreatic NET and 15.0% (6/40) in extra-pancreatic NET, and an overall disease control rate (“DCR”) of 91.4%. Median overall progression-free survival (“PFS”) has not been reached, but is estimated to be 16.6 months (95% CI: 13.4, 19.4) with longer median PFS in pancreatic NET estimated at 19.4 months and shorter median PFS in extra-pancreatic NET estimated at 13.4 months. Importantly, there were 12 patients who had progressed after treatment with targeted therapies (e.g. sunitinib and everolimus) and all benefited from sulfatinib treatment (3 PRs and 9 SDs). Sulfatinib was well tolerated with Grade ≥3 adverse events (AEs) with >5% incidence, regardless of causality, of hypertension (31%), proteinuria (14%), hyperuricemia (10%), hypertriglyceridemia (9%), diarrhea (7%) and ALT increase (6%). Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02267967.
Based on the promising Phase I and Phase II efficacy data and tolerability in patients with advanced NETs, two randomized Phase III trials are ongoing.