The INTERNET STUDY: A phase II study of everolimus in patients with fluorodeoxyglucose ( 18 18 F) positron‐emission tomography positive intermediate grade pancreatic neuroendocrine tumors

摘要

Abstract Aims This multicenter phase II trial evaluates the efficacy of everolimus in poor prognosis grade 2 (G2) pancreatic neuroendocrine tumors (PNETs), defined by 2‐[fluorine‐18]fluoro‐2‐deoxy‐d‐glucose (FDG) positron‐emission tomography (PET) avidity. FDG–PET avidity in NETs is associated with a significantly higher risk of death, outperforming Ki‐67 index or liver metastases as a poor prognostic factor. We hypothesized that everolimus has efficacy in patients with FDG–PET‐avid G2 PNETs and prospectively evaluated progression‐free survival (PFS) and response in the first‐line setting. Methods Patients with FDG–PET‐avid G2 advanced PNET received everolimus 10?mg daily until disease progression. Patients were staged every 12?weeks with CT/MRI and FDG–PET and every 24?weeks with Gallium 68 (68Ga) 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)–octreotate (DOTATATE, GaTate) PET. The primary endpoint was PFS at 6 months. Overall survival rate, PET/structural imaging response and toxicity were also measured. Results Nine patients were accrued from December 2012 to February 2015. Median treatment duration was 13.8 months. The estimated PFS rate at 6 months was 78%. The best response on CT/MRI was stable disease in nine patients (100%) and partial response on FDG–PET in five patients (55.5%). Treatment‐related adverse effects were consistent with previous studies of everolimus. Conclusion Everolimus is active with prolonged disease control in poor prognosis FDG‐avid G2 PNETs. Treatment individualization based on functional imaging warrants further evaluation.