Efficacy of aflibercept with FOLFOX and maintenance with fluoropyrimidine as first‑line therapy for metastatic colorectal cancer: GERCOR VELVET phase II study

Chibaudel,Benoist; Bachet,Jean‑Baptiste; André,Thierry; Auby,Dominique; Desramé,Jérôme; Deplanque,Gaël; Lecaille,Cédric; Louvet,Christophe; Tournigand,Christophe; Lebrun‑Ly,Valérie; Dauba,Jérôme; Lledo,Gérard; Garcia,Marie‑Line; Dubreuil,Olivier; Hamed,Nabil   Baba; Meurisse,Aurélia; Larsen,Annette  K.; Tijeras‑Raballand,Annemilaï; Bonnetain,Franck; De Gramont,Aimery

doi:10.3892/ijo.2019.4709

Efficacy of aflibercept with FOLFOX and maintenance with fluoropyrimidine as first‑line therapy for metastatic colorectal cancer: GERCOR VELVET phase II study

Authors:
- Benoist Chibaudel
- Jean‑Baptiste Bachet
- Thierry André
- Dominique Auby
- Jérôme Desramé
- Gaël Deplanque
- Cédric Lecaille
- Christophe Louvet
- Christophe Tournigand
- Valérie Lebrun‑Ly
- Jérôme Dauba
- Gérard Lledo
- Marie‑Line Garcia
- Olivier Dubreuil
- Nabil Baba Hamed
- Aurélia Meurisse
- Annette K. Larsen
- Annemilaï Tijeras‑Raballand
- Franck Bonnetain
- Aimery De Gramont
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Affiliations: Department of Medical Oncology, Franco‑British Institute, 92300 Levallois‑Perret, France, Department of Gastroenterology, Sorbonne University, Pierre and Marie Curie University Paris 6, CH Universitaire Pitié‑Salpétrière, 75013 Paris, France, Department of Medical Oncology, Sorbonne University, Hospital Saint‑Antoine, 75012 Paris, France, Department of Medical Oncology, CH de Mont‑de‑Marsan, Hospital Layné, 40024 Mont‑de‑Marsan, France, Department of Gastroenterology, Private Hospital Jean Mermoz, 69008 Lyon, France, Department of Medical Oncology, Hospital Saint‑Joseph, 75014 Paris, France, Department of Medical Oncology, Polyclinic Bordeaux Nord, 33300 Bordeaux, France, Department of Medical Oncology, Institut Mutualiste Montsouris, 75014 Paris, France, Department of Medical Oncology, Henri Mondor Hospital, 94010 Créteil, France, CHU Dupuytren, 87042 Limoges, France, Centre de Recherche Saint‑Antoine, INSERM U938, Hospital Saint‑Antoine, 75012 Paris, France, Department of Gastroenterology, Hospital Pitié‑Salpétrière, 75013 Paris, France, Department of Biostatistics, CHU Besançon, 25030 Besançon, France, Cancer Biology and Therapeutics, Centre de Recherche Saint‑Antoine, INSERM U938, Sorbonne Université Faculté de Médecine, 75012 Paris, France, Preclinical and Translational Laboratory, AFR Oncology, Paris, France
Published online on: February 1, 2019 https://doi.org/10.3892/ijo.2019.4709
Pages: 1433-1445

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Abstract

Aflibercept in combination with 5‑fluorouracil (5‑FU)/irinotecan improves overall survival in the second‑line therapy of patients with metastatic colorectal cancer (mCRC). In this study, we evaluated the effects of aflibercept in first‑line therapy with FOLFOX followed by maintenance with fluoropyrimidine. VELVET was a prospective, single‑arm multicenter phase II study (completed). Patients with previously untreated, unresectable, evaluable or measurable mCRC, with an age ≥18 years, and an ECOG performance status of 0‑2 received 6 cycles of modified FOLFOX7 (5‑FU/folinic acid and oxaliplatin) with aflibercept at 4 mg/kg every 2 weeks followed by maintenance therapy with fluoropyrimidine with aflibercept until disease progression or limiting toxicity. The reintroduction of oxaliplatin was performed at first progression. The primary endpoint was progression‑free survival (PFS) at 6 months. From May, 2013 to May, 2014, 49 patients were included and 48 were evaluable for response. In total, 33 patients (67.4%) were alive without progression at 6 months. The Kaplan‑Meier survival 6‑month and 1‑year PFS rates were 79.1 and 36.1%, respectively, and the median PFS was 9.3 months (95% CI, 8.3‑12.5). The objective response rate was 59.2% (N=29/49). The most common (≥10%) grade 3‑4 adverse events were hypertension (23%), fatigue (15%), neutropenia (12%), neuropathy (12%) and stomatitis (10%). Three (6%) treatment‑related deaths occurred: One from stroke, one from pulmonary embolism and one from neutropenic sepsis. On the whole, this study demonstrates the efficacy of aflibercept in combination with an oxaliplatin‑based regimen in the first‑line therapy of patients with mCRC. A strict monitoring of blood pressure and immediate management of hypertension during therapy is mandatory.

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