PMID- 27091810 OWN - NLM STAT- MEDLINE DCOM- 20171227 LR - 20200206 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 27 IP - 7 DP - 2016 Jul TI - 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. PG - 1273-9 LID - 10.1093/annonc/mdw176 [doi] AB - BACKGROUND: 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 AND METHODS: 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. RESULTS: 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%). CONCLUSION: 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. CLINICAL TRIAL NUMBER: NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41. CI - (c) The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Folprecht, G AU - Folprecht G AD - Medical Department I, University Cancer Center, University Hospital Carl Gustav Carus, Dresden, Germany gunnar.folprecht@uniklinikum-dresden.de. FAU - Pericay, C AU - Pericay C AD - Hospital de Sabadell, Corporacio Sanitaria Parc Tauli-Institut Universitari, Sabadell, Spain. FAU - Saunders, M P AU - Saunders MP AD - Department of Radiotherapy and Oncology, The Christie NHS Foundation Trust, Manchester. FAU - Thomas, A AU - Thomas A AD - Department of Cancer Studies, University of Leicester, Leicester, UK. FAU - Lopez Lopez, R AU - Lopez Lopez R AD - Department of Medical Oncology, Hospital Clinico Universitario e Instituto de Investigacion, Santiago de Compostela, Spain. FAU - Roh, J K AU - Roh JK AD - Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Chistyakov, V AU - Chistyakov V AD - Pyatigorsk Cancer Dispensary, Stavropol, Russia. FAU - Hohler, T AU - Hohler T AD - Department I of Internal Medicine, Prosper Hospital, Recklinghausen, Germany. FAU - Kim, J-S AU - Kim JS AD - Department of Oncology and Hematology, Korea University Guro Hospital, Seoul, Republic of Korea. FAU - Hofheinz, R-D AU - Hofheinz RD AD - Department III of Internal Medicine, University Hospital, Mannheim, Germany. FAU - Ackland, S P AU - Ackland SP AD - Department of Medical Oncology, Calvary Mater Hospital, Newcastle Hunter Medical Research Institute and University of Newcastle, Callaghan, Australia. FAU - Swinson, D AU - Swinson D AD - Department of Oncology, St James' Hospital, Leeds, UK. FAU - Kopp, M AU - Kopp M AD - Samara Regional Oncology Dispensary, Samara. FAU - Udovitsa, D AU - Udovitsa D AD - Oncological Dispensary #2, Sochi, Russia. FAU - Hall, M AU - Hall M AD - Cancer Services Division, Mount Vernon Cancer Centre, Middlesex. FAU - Iveson, T AU - Iveson T AD - Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK. FAU - Vogel, A AU - Vogel A AD - Clinic of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. FAU - Zalcberg, J R AU - Zalcberg JR AD - School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. LA - eng SI - ClinicalTrials.gov/NCT00851084 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20160418 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Organoplatinum Compounds) RN - 0 (Recombinant Fusion Proteins) RN - 04ZR38536J (Oxaliplatin) RN - 15C2VL427D (aflibercept) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) RN - Q573I9DVLP (Leucovorin) RN - U3P01618RT (Fluorouracil) RN - Folfox protocol SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects MH - Colorectal Neoplasms/*drug therapy/pathology MH - Disease-Free Survival MH - Drug-Related Side Effects and Adverse Reactions/pathology MH - Female MH - Fluorouracil/*administration & dosage/adverse effects MH - Humans MH - Leucovorin/administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Organoplatinum Compounds/*administration & dosage/adverse effects MH - Oxaliplatin MH - Receptors, Vascular Endothelial Growth Factor/*administration & dosage MH - Recombinant Fusion Proteins/*administration & dosage OTO - NOTNLM OT - aflibercept OT - angiogenesis OT - colorectal cancer OT - mFOLFOX6 OT - oxaliplatin EDAT- 2016/04/20 06:00 MHDA- 2017/12/28 06:00 CRDT- 2016/04/20 06:00 PHST- 2015/08/19 00:00 [received] PHST- 2016/04/10 00:00 [accepted] PHST- 2016/04/20 06:00 [entrez] PHST- 2016/04/20 06:00 [pubmed] PHST- 2017/12/28 06:00 [medline] AID - S0923-7534(19)35699-6 [pii] AID - 10.1093/annonc/mdw176 [doi] PST - ppublish SO - Ann Oncol. 2016 Jul;27(7):1273-9. doi: 10.1093/annonc/mdw176. Epub 2016 Apr 18.