Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer

• Verfasst von: Folprecht, Gunnar [VerfasserIn]
• Verfasst von: Hofheinz, Ralf-Dieter [VerfasserIn]
• Titel: Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer
• Titelzusatz: the AFFIRM study
• Verf.angabe: G. Folprecht, C. Pericay, M.P. Saunders, A. Thomas, R. Lopez Lopez, J.K. Roh, V. Chistyakov, T. Höhler, J.-S. Kim, R.-D. Hofheinz, S.P. Ackland, D. Swinson, M. Kopp, D. Udovitsa, M. Hall, T. Iveson, A. Vogel and J.R. Zalcberg
• E-Jahr: 2016
• Jahr: 18 April 2016
• Umfang: 7 S.
• Fussnoten: Gesehen am 18.01.2018
• Titel Quelle: Enthalten in: Annals of oncology
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1990
• Jahr Quelle: 2016
• Band/Heft Quelle: 27(2016), 7, Seite 1273-1279
• ISSN Quelle: 1569-8041
• DOI: doi:10.1093/annonc/mdw176
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 156732469X

Abstract

BackgroundThe 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 and methodsPatients 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.ResultsOf 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%).ConclusionNo 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.Clinical Trial NumberNCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.