Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumour: A phase II study of Spanish Neuroendocrine Tumour Group (GETNE0801) |
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Authors: | Daniel Castellano Jaume Capdevila Javier Sastre Vicente Alonso Marta Llanos Rocío García-Carbonero José Luis Manzano Mozo Isabel Sevilla Ignacio Durán Ramón Salazar |
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Institution: | 1. Hospital Universtitario 12 de Octubre, Spain;2. Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Spain;3. Hospital Clínico San Carlos, Center affiliated to the Red Temática de Investigación Cooperativa (RD06/0020/0021), Instituto Carlos III, Spanish Ministry of Science and Innovation, Spain;4. Hospital Miguel Servet, Spain;5. Hospital Universitario de Canarias, Spain;6. Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Spain;7. Hospital Universitari Germans Trias i Pujol, Spain;8. Hospital Clínico Universitario Virgen de la Victoria, Spain;9. Hospital Madrid-Norte Sanchinarro, Spain;10. Institut Català d’Oncología, Spain |
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Abstract: | BackgroundSorafenib and bevacizumab as single agents have shown efficacy and acceptable toxicity in NETs phase II trials. Sorafenib and bevacizumab combination has shown manageable toxicity in phase I trials in solid tumours. The purpose of this study was to evaluate the safety and efficacy of the combination of sorafenib and bevacizumab in patients with advanced neuroendocrine tumours.MethodsOpen-label, uncontrolled, multicenter, phase II clinical trial. Eligibility criteria: age ? 18 years, histologically confirmed measurable advanced NETs; 1 prior chemotherapy allowed; ECOG-PS 0–2. Patients were treated during 6 months and followed up for an additional 6 months. Treatment: sorafenib 200 mg bid (days 1–5 of each week) and bevacizumab 5 mg/kg once every 2 weeks (day 1, week 1). Tumour response was performed according to RECIST (v1.0) every 2 months during the treatment period. Adverse events were graded according to CTCAE (v3.0).Findings44 Patients enrolled, 59.1% men, median age 60 years (range 32–76). 70.5% carcinoid tumours, 29.5% pancreatic tumour. Baseline target lesions mainly in the liver (86.4%). Global PFSR was 90.9% (91.7% carcinoid tumours and 88.9% pancreatic tumours). Median PFS was 12.4 months, median TTP was 14.5 months, ORR was 9.4% and DCR was 95.1%. Most common grade 3–4 toxicities: asthenia (11.4%) and hand–foot skin reaction (15.9%).InterpretationSorafenib and bevacizumab combination showed clinical benefit but unfavourable safety results compared with drugs in monotherapy. Further development of this combination is not warranted and a sequential approach is recommended instead. |
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Keywords: | Targeted therapy Sorafenib Bevacizumab |
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