Mei Sim Lung1,2, Rodney J Hicks1,3,4, Nick Pavlakis5, Emma Link4,6, Michael Jefford1,2,4, Benjamin Thomson1,7, David K Wyld8,9, Winston Liauw10, Timothy Akhurst1,3,4, Narmatha Kuru6, Michael Michael1,2,4. 1. Neuroendocrine Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 2. Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 3. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia. 5. Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia. 6. Biostatistics and Clinical Trials Centre, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre Building, Melbourne, VIC, Australia. 7. University of Melbourne Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia. 8. Department of Medical Oncology, Royal Brisbane and Women's Hospital, QLD, Australia. 9. School of Medicine, University of Queensland, QLD, Australia. 10. Department of Medical Oncology, Cancer Care Centre, Kogarah, NSW, Australia.
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 receivedeverolimus 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.
RCT Entities:
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.
Authors: M Rinzivillo; D Prosperi; F Mazzuca; L Magi; E Iannicelli; E Pilozzi; G Franchi; A Laghi; B Annibale; A Signore; F Panzuto Journal: J Endocrinol Invest Date: 2020-08-07 Impact factor: 4.256