- 作者：Daniel Castellano ; Jaume Capdevila ; Javier Sastre ; Vicente Alonso ; Marta Llanos ; Roc铆o Garc铆a-Carbonero ; Jos茅 Luis Manzano Mozo ; Isabel Sevilla ; Ignacio Dur谩n ; Ram贸n Salazar
- 关键词：Targeted therapy ; Sorafenib ; Bevacizumab
- 刊名：European Journal of Cancer
- 出版年：December, 2013
- 年：2013
- 卷：49
- 期：18
- 页码：3780-3787
- 全文大小：697 K
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. Eligibility criteria: age 猢?#xA0;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).
Findings
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%).
Interpretation
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.