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

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.