Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study
- 18 April 2016
- journal article
- research article
- Published by Elsevier BV in Annals of Oncology
- Vol. 27 (7), 1273-1279
- https://doi.org/10.1093/annonc/mdw176
Abstract
The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2–34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.Keywords
Funding Information
- Sanofi
- Regeneron Pharmaceuticals, Inc.
- Dr George Xinarianos
- Regeneron Pharmaceuticals, Inc
- Sanofi
- Regeneron Pharmaceuticals, Inc.
- Dr George Xinarianos
- Regeneron Pharmaceuticals, Inc
This publication has 22 references indexed in Scilit:
- Evaluation of efficacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the first-line settingBritish Journal of Cancer, 2015
- Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upAnnals of Oncology, 2014
- Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: Prespecified subgroup analyses from the VELOUR trialEuropean Journal of Cancer, 2013
- Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trialThe Lancet Oncology, 2013
- Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based RegimenJournal of Clinical Oncology, 2012
- Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumabAngiogenesis, 2012
- Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III StudyJournal of Clinical Oncology, 2008
- Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200Journal of Clinical Oncology, 2007
- Combined Analysis of Efficacy: The Addition of Bevacizumab to Fluorouracil/Leucovorin Improves Survival for Patients With Metastatic Colorectal CancerJournal of Clinical Oncology, 2005
- Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal CancerThe New England Journal of Medicine, 2004