title: Aflibercept Plus FOLFIRI vs. Placebo Plus FOLFIRI in Second-Line Metastatic Colorectal Cancer: a Post Hoc Analysis of Survival from the Phase III VELOUR Study Subsequent to Exclusion of Patients who had Recurrence During or Within 6 Months of Completing Adjuvant Oxaliplatin-Based Therapy.
abstract: The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6 months of completion of oxaliplatin-containing adjuvant chemotherapy (N = 124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population (N = 1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population (N = 1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95 % confidence interval (CI) 0.68-0.90; median survival difference 1.87 months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95 % CI 0.63-1.04; median survival difference 2.14 months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-naïve patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns.
authors.affiliation: Digestive Oncology, University Hospitals Gasthuisberg/Leuven, Leuven, Belgium. Eric.VanCutsem@uzleuven.be.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Sanofi, Chilly Mazarin, France.
authors.forename: Florence
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authors.lastname: Joulain
authors.affiliation: Centro De Oncologia, Hospital Sirio Libanes, São Paulo, Brazil.
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authors.affiliation: Kimmel Cancer Center at Jefferson, Jefferson University Hospitals, Philadelphia, PA, USA.
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authors.affiliation: Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Paul
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authors.affiliation: The Royal Marsden Hospital (Surrey), Sutton, Surrey, UK.
authors.forename: David
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authors.affiliation: Department of Medical Oncology, Tumor Biology Center, Freiburg, Germany.
authors.forename: Dirk
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authors.lastname: Arnold
authors.affiliation: Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
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authors.affiliation: Amphia Hospital, Breda, The Netherlands.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Ten Tije
authors.affiliation: Monash University, Melbourne, Victoria, Australia.
authors.forename: Joseph
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authors.lastname: McKendrick
authors.affiliation: Schwerpunktpraxis für Hämatologie und Onkologie, Magdeburg, Germany.
authors.forename: Hendrik
authors.initials: H
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authors.affiliation: St-Luc University Hospital, Brussels, Belgium.
authors.forename: Yves
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authors.affiliation: Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grávalos
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authors.forename: Solenn
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authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
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authors.lastname: Andria
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authors.forename: Emmanuelle
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authors.lastname: Dochy
authors.affiliation: Sanofi Global Oncology Medical Affairs, Cambridge, MA, USA.
authors.forename: Raghu L
authors.initials: RL
authors.lastname: Vishwanath
authors.affiliation: Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Macarulla
authors.affiliation: Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077150:Oxaliplatin; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011993:Recombinant Fusion Proteins; D000077150:Oxaliplatin; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin