title: Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumour: a phase II study of Spanish Neuroendocrine Tumour Group (GETNE0801).
abstract: BACKGROUND
  Sorafenib 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.
  
  
  METHODS
  Open-label, uncontrolled, multicenter, phase II clinical trial.
  
  
  METHODS
  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.
  
  
  METHODS
  sorafenib 200mg bid (days 1-5 of each week) and bevacizumab 5mg/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).
  
  
  RESULTS
  44 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%).
  
  
  CONCLUSIONS
  Sorafenib 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.
authors.affiliation: Hospital Universtitario 12 de Octubre, Spain. Electronic address: cdanicas@hotmail.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso
authors.forename: Marta
authors.initials: M
authors.lastname: Llanos
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Carbonero
authors.forename: José Luis
authors.initials: JL
authors.lastname: Manzano Mozo
authors.forename: Isabel
authors.initials: I
authors.lastname: Sevilla
authors.forename: Ignacio
authors.initials: I
authors.lastname: Durán
authors.forename: Ramón
authors.initials: R
authors.lastname: Salazar
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D000068258:Bevacizumab; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077157:Sorafenib; D013030:Spain; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010671:Phenylurea Compounds; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib
keywords: Bevacizumab; Sorafenib; Targeted therapy