Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302) |
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| Institution: | 1. Department of Gastroenterology and Digestive Oncology, Hopital European George Pompidou, Paris, France;2. HepatoGastroenterology and Digestive Oncology Department, CHU La Timone, Marseille, France;3. Biostatistics, FFCD, EPICAD INSERM LNC-UMR1231, University of Burgundy and Franche Comté, Dijon, France;4. HepatoGastroenterology Department, Avicenne Hospital, Bobigny, France;5. HepatoGastroenterology Department, Saint-Louis Hospital, Paris, France;6. Gastroenterology Department, CHU Angers, Angers, France;7. HepatoGastroenterology Department, Trousseau Hospital, Tours, France;8. HepatoGastroenterology Department, Pitié-Salpêtrière Hospital, Paris, France;9. HepatoGastroenterology Department, Bicêtre Hospital, Paris, France;10. Jean-Mermoz Private Hospital, Cancerology Institute, Lyon, France;11. HepatoGastroenterology and Digestive Oncology Department, University Hospital Dijon, University of Burgundy and Franche Comté, FFCD, EPICAD INSERM LNC-UMR 1231, Dijon, France;1. College of Medicine, University of South Florida, Tampa, Florida;2. Department of Radiation Oncology, H Lee Moffitt Cancer Center, Tampa, Florida;3. Department of Radiation Oncology, Case Western Reserve University School of Medicine, and Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio;1. Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada;2. Department of Oncology, University of Calgary, Calgary, Alberta, Canada;1. Division of Thoracic Oncology, Department of Medical Oncology, Tochigi Cancer Center, Tochigi, Japan;2. Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital and Regional Cancer Center, Ibaraki, Japan;3. Department of Thoracic Diseases, Division of Thoracic Oncology, Tsuboi Cancer Center Hospital, Fukushima, Japan;1. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;2. Department of Respiratory, Xiangya Hospital, Central South University, Changsha, China;3. Department of Respiratory, Xijing Hospital, the First Affiliated Hospital of the Fourth Military University, Xi-an, China;4. Division of Thoracic Tumor, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China;5. Department of Respiratory, Nanjing Military General Hospital, Nanjing, China;6. Division of Thoracic Tumor, the First Affiliated Hospital, Zhejiang University, Hangzhou, China;7. Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China;8. Department of Medical Oncology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China;9. Division of Thoracic Tumor, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, China;10. Division of Thoracic Tumor, Beijing Cancer Hospital, Beijing University, Beijing, China;11. Division of Thoracic Tumor, Guangxi Cancer Hospital, Nanning, China;12. Division of Thoracic Tumor, Beijing Chest Hospital, Capital Medical University, Beijing, China;1. Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;2. Department of General Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;3. Office of Protocol Support and Management, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;4. Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA |
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| Abstract: | BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H0: 55% and H1= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction. |
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| Keywords: | Antiangiogenic therapy Antineoplasic drug Colon cancer Metastases Targeted therapy |
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