Journal ArticleDOI
Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial
Aimery de Gramont,Eric Van Cutsem,Hans-Joachim Schmoll,Josep Tabernero,Stephen Clarke,Malcolm J. Moore,David Cunningham,Thomas H. Cartwright,J. Randolph Hecht,Fernando Rivera,Seock-Ah Im,György Bodoky,Ramon Salazar,F. Maindrault-Goebel,Einat Shacham-Shmueli,Emilio Bajetta,Martina Makrutzki,A. Shang,Thierry André,Paulo M. Hoff +19 more
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TLDR
The primary endpoint was disease-free survival, analysed for all randomised patients with stage III disease, and the most common grade 3-5 adverse events were neutropenia.Abstract:
Summary Background Bevacizumab improves the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer. Our aim was to assess the use of bevacizumab in combination with oxaliplatin-based chemotherapy in the adjuvant treatment of patients with resected stage III or high-risk stage II colon carcinoma. Methods Patients from 330 centres in 34 countries were enrolled into this phase 3, open-label randomised trial. Patients with curatively resected stage III or high-risk stage II colon carcinoma were randomly assigned (1:1:1) to receive FOLFOX4 (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , and fluorouracil 400 mg/m 2 bolus plus 600 mg/m 2 22-h continuous infusion on day 1; leucovorin 200 mg/m 2 plus fluorouracil 400 mg/m 2 bolus plus 600 mg/m 2 22-h continuous infusion on day 2) every 2 weeks for 12 cycles; bevacizumab 5 mg/kg plus FOLFOX4 (every 2 weeks for 12 cycles) followed by bevacizumab monotherapy 7·5 mg/kg every 3 weeks (eight cycles over 24 weeks); or bevacizumab 7·5 mg/kg plus XELOX (oxaliplatin 130 mg/m 2 on day 1 every 2 weeks plus oral capecitabine 1000 mg/m 2 twice daily on days 1–15) every 3 weeks for eight cycles followed by bevacizumab monotherapy 7·5 mg/kg every 3 weeks (eight cycles over 24 weeks). Block randomisation was done with a central interactive computerised system, stratified by geographic region and disease stage. Surgery with curative intent occurred 4–8 weeks before randomisation. The primary endpoint was disease-free survival, analysed for all randomised patients with stage III disease. This study is registered with ClinicalTrials.gov, number NCT00112918. Findings Of the total intention-to-treat population (n=3451), 2867 patients had stage III disease, of whom 955 were randomly assigned to receive FOLFOX4, 960 to receive bevacizumab–FOLFOX4, and 952 to receive bevacizumab–XELOX. After a median follow-up of 48 months (range 0–66 months), 237 patients (25%) in the FOLFOX4 group, 280 (29%) in the bevacizumab–FOLFOX4 group, and 253 (27%) in the bevacizumab–XELOX group had relapsed, developed a new colon cancer, or died. The disease-free survival hazard ratio for bevacizumab–FOLFOX4 versus FOLFOX4 was 1·17 (95% CI 0·98–1·39; p=0·07), and for bevacizumab–XELOX versus FOLFOX4 was 1·07 (0·90–1·28; p=0·44). After a minimum follow-up of 60 months, the overall survival hazard ratio for bevacizumab–FOLFOX4 versus FOLFOX4 was 1·27 (1·03–1·57; p=0·02), and for bevacizumab–XELOX versus FOLFOX4 was 1·15 (0·93–1·42; p=0·21). The 573 patients with high-risk stage II cancer were included in the safety analysis. The most common grade 3–5 adverse events were neutropenia (FOLFOX4: 477 [42%] of 1126 patients, bevacizumab-FOLFOX4: 416 [36%] of 1145 patients, and bevacizumab–XELOX: 74 [7%] of 1135 patients), diarrhoea (110 [10%], 135 [12%], and 181 [16%], respectively), and hypertension (12 [1%], 122 [11%], and 116 [10%], respectively). Serious adverse events were more common in the bevacizumab groups (bevacizumab–FOLFOX4: 297 [26%]; bevacizumab–XELOX: 284 [25%]) than in the FOLFOX4 group (226 [20%]). Treatment-related deaths were reported in one patient receiving FOLFOX4, two receiving bevacizumab–FOLFOX4, and five receiving bevacizumab–XELOX. Interpretation Bevacizumab does not prolong disease-free survival when added to adjuvant chemotherapy in resected stage III colon cancer. Overall survival data suggest a potential detrimental effect with bevacizumab plus oxaliplatin-based adjuvant therapy in these patients. On the basis of these and other data, we do not recommend the use of bevacizumab in the adjuvant treatment of patients with curatively resected stage III colon cancer. Funding Genentech, Roche, and Chugai.read more
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Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer
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Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology
Al B. Benson,Alan P. Venook,Lynette Cederquist,Emily Chan,Yi-Jen Chen,Harry S. Cooper,Dustin A. Deming,Paul F. Engstrom,Peter C. Enzinger,Alessandro Fichera,Jean L. Grem,Axel Grothey,Howard S. Hochster,Sarah E. Hoffe,Steven C. Hunt,Ahmed Kamel,Natalie Kirilcuk,Smitha S. Krishnamurthi,Wells A. Messersmith,Mary F. Mulcahy,James D. Murphy,Steven J. Nurkin,Leonard B. Saltz,Sunil Sharma,David Shibata,John M. Skibber,Constantinos T. Sofocleous,Elena M. Stoffel,Eden Stotsky-Himelfarb,Christopher G. Willett,Christina Wu,Kristina M. Gregory,Deborah A. Freedman-Cass +32 more
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R. Labianca,Bernard Nordlinger,Giordano D. Beretta,Stefania Mosconi,Mario Mandalà,Andrés Cervantes,Dirk Arnold +6 more
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Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
A. de Gramont,A. Figer,M. Seymour,M. Homerin,A. Hmissi,J. Cassidy,Corrado Boni,H. Cortes-Funes,Andrés Cervantes,Gilles Freyer,Demetris Papamichael,N. Le Bail,C. Louvet,D. Hendler,F. de Braud,C. Wilson,Francois Morvan,Andrea Bonetti +17 more
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Journal ArticleDOI
Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
Eric Van Cutsem,Claus Henning Köhne,Erika Hitre,J. Zaluski,Chung Rong Chang Chien,A. Makhson,Geert R. D'Haens,Tamás Pintér,Robert Lim,György Bodoky,Jae Kyung Roh,Gunnar Folprecht,Paul Ruff,Christopher Stroh,Sabine Tejpar,Michael Schlichting,Johannes Nippgen,Philippe Rougier +17 more
TL;DR: In this paper, the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer was investigated.
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Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer
Thierry André,Corrado Boni,Lamia Mounedji-Boudiaf,Matilde Navarro,Josep Tabernero,Tamas Hickish,C. Topham,Marta Zaninelli,Phillip Clingan,John Bridgewater,Isabelle Tabah-Fisch,Aimery de Gramont +11 more
TL;DR: Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer.
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