%0 Generic %A A., Pellat %A C., Dreyer %A C., Couffignal %A T., Walter %A C., Lombard-Bohas %A P., Niccoli %A J.F., Seitz %A O., Hentic %A T., André %A R., Coriat %A S., Faivre %A M., Zappa %A P., Ruszniewski %A N., Pote %A A., Couvelard %A E., Raymond %D 2018 %T Supplementary Material for: Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Clinical_and_Biomarker_Evaluations_of_Sunitinib_in_Patients_with_Grade_3_Digestive_Neuroendocrine_Neoplasms/5960992 %R 10.6084/m9.figshare.5960992.v1 %2 https://ndownloader.figshare.com/files/10683157 %2 https://ndownloader.figshare.com/files/10683163 %2 https://ndownloader.figshare.com/files/10683166 %2 https://ndownloader.figshare.com/files/10683169 %K Sunitinib %K Grade 3 neuroendocrine neoplasms %K p-AKT %K Ki-67 %X Background/Aims: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. Methods: Sunitinib was given at a dose of 37.5 mg/day as a continuous daily dosing until progression or unacceptable toxicity. Evaluation of activity was based on RECIST1.1. Safety was evaluated according to NCI-CTCAE v4. Pharmacokinetics of sunitinib and its main active metabolite SU12662 were evaluated. All tumour samples were reviewed histologically for tumour differentiation. PDGFRβ, carbonic anhydrase 9, Ki-67, VEGFR2, and p-AKT were quantified using immunohistochemistry and their expression correlated with response by RECIST1.1. Results: Thirty-one patients were included and 26 had available histological tissue. Six and 20 patients presented well-differentiated tumours (NET-G3) and neuroendocrine carcinoma (NEC), respectively. Eighteen patients responded to sunitinib (4 experienced partial responses and 14 tumour stabilization). A high p-AKT expression correlated with lower response to sunitinib (OR 0.94, 95% CI 0.89–0.99, p = 0.04). Safety and PK exposure to sunitinib and SU12662 in these patients were consistent with that reported in PanNET. Conclusion: Sunitinib showed evidence of activity in patients with GEPNEN-G3 with expected toxicity profile. In the NET-G3 and NEC groups, 4/6 and 11/20 patients were responders, respectively. High p-AKT expression predicted a lower response to sunitinib. Our study allowed the identification of a potential biomarker of resistance/sensitivity to sunitinib in aggressive GEPNEN-G3. %I Karger Publishers