Emmanuel Mitry1, Thomas Walter2, Eric Baudin3, Jean-Emmanuel Kurtz4, Philippe Ruszniewski5, Sophie Dominguez-Tinajero6, Leïla Bengrine-Lefevre7, Guillaume Cadiot8, Clarisse Dromain9, Françoise Farace10, Philippe Rougier11, Michel Ducreux12. 1. Medical Oncology Department, Curie Institute, Paris, France. Electronic address: emmanuel.mitry@curie.net. 2. Medical Oncology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: thomas.walter@chu-lyon.fr. 3. Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy Institute, Villejuif, France. Electronic address: Eric.BAUDIN@igr.fr. 4. Hematology and Oncology Department, University Hospital, Strasbourg, France. Electronic address: J-Emmanuel.KURTZ@chru-strasbourg.fr. 5. Gastroenterology and Pancreatology Department, Beaujon Hospital, Clichy, France. Electronic address: philippe.ruszniewski@bjn.aphp.fr. 6. Hematology and Oncology Department, Oscar Lambret Center, Lille, France. Electronic address: Dominguez.Sophie@ghicl.net. 7. Medical Oncology Department, Saint-Antoine Hospital, Bordeaux, France. Electronic address: leila.bengrine-lefevre@sat.aphp.fr. 8. Hepato-Gastroenterology and Digestive Oncology Department, Robert Debré Hospital, Reims, France. Electronic address: gcadiot@chu-reims.fr. 9. Radio Diagnostic Department, Gustave Roussy Institute, Villejuif, France. Electronic address: dromain@igr.fr. 10. Laboratory of Translational Research, Gustave Roussy Institute, Villejuif, France. Electronic address: francoise.farace@igr.fr. 11. Hepato-Gastroenterology and Digestive Oncology Department, Georges Pompidou European Hospital, Université Paris V, Paris, France. Electronic address: philippe.rougier@egp.aphp.fr. 12. Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France. Electronic address: Michel.DUCREUX@igr.fr.
Abstract
AIM OF THE STUDY: Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients. PATIENTS AND METHODS: BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate <15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life. RESULTS: Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was <15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%). CONCLUSION: The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial.
AIM OF THE STUDY: Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients. PATIENTS AND METHODS: BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate <15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life. RESULTS: Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was <15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%). CONCLUSION: The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial.
Authors: James C Yao; Katherine A Guthrie; Cesar Moran; Jonathan R Strosberg; Matthew H Kulke; Jennifer A Chan; Noelle LoConte; Robert R McWilliams; Edward M Wolin; Bassam Mattar; Shannon McDonough; Helen Chen; Charles D Blanke; Howard S Hochster Journal: J Clin Oncol Date: 2017-04-06 Impact factor: 44.544
Authors: Timothy P Pearman; Jennifer L Beaumont; David Cella; Maureen P Neary; James Yao Journal: Support Care Cancer Date: 2016-03-31 Impact factor: 3.603