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 ≥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 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). 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.
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 ≥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 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). 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.
Authors: J Capdevila; O Casanovas; R Salazar; D Castellano; A Segura; P Fuster; J Aller; R García-Carbonero; P Jimenez-Fonseca; E Grande; J P Castaño Journal: Oncogene Date: 2016-09-19 Impact factor: 9.867
Authors: Robert A Ramirez; Aman Chauhan; Juan Gimenez; Katharine E H Thomas; Ioni Kokodis; Brianne A Voros Journal: Rev Endocr Metab Disord Date: 2017-12 Impact factor: 6.514
Authors: David M Hyman; Naiyer Rizvi; Ronald Natale; Deborah K Armstrong; Michael Birrer; Lawrence Recht; Efrat Dotan; Vicky Makker; Thomas Kaley; Denison Kuruvilla; Matthew Gribbin; Jennifer McDevitt; Dominic W Lai; Mohammed Dar Journal: Clin Cancer Res Date: 2018-03-20 Impact factor: 12.531