Journal ArticleDOI
Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial
Jaafar Bennouna,Javier Sastre,Dirk Arnold,Pia Österlund,Richard Greil,Eric Van Cutsem,Roger von Moos,Jose María Vieitez,Olivier Bouché,Christophe Borg,Claus-Christoph Steffens,V. Alonso-Orduna,Christoph Schlichting,Irmarie Reyes-Rivera,Belguendouz Bendahmane,Thierry André,Stefan Kubicka +16 more
TLDR
Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer.Abstract:
Summary Background Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line metastatic colorectal cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-based treatment. Methods In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged ≥18 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2·5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7·5 mg/kg every 3 weeks, intravenously). The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). A combination of a permuted block design and the Pocock and Simon minimisation algorithm was used for the randomisation. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00700102. Findings Between Feb 1, 2006, and June 9, 2010, 409 (50%) patients were assigned to bevacizumab plus chemotherapy and 411 (50%) to chemotherapy alone. Median follow-up was 11·1 months (IQR 6·4–15·6) in the bevacizumab plus chemotherapy group and 9·6 months (5·4–13·9) in the chemotherapy alone group. Median overall survival was 11·2 months (95% CI 10·4–12·2) for bevacizumab plus chemotherapy and 9·8 months (8·9–10·7) for chemotherapy alone (hazard ratio 0·81, 95% CI 0·69–0·94; unstratified log-rank test p=0·0062). Grade 3–5 bleeding or haemorrhage (eight [2%] vs one [ vs three [ vs 12 [3%]) were more common in the bevacizumab plus chemotherapy group than in the chemotherapy alone group. The most frequently reported grade 3–5 adverse events were neutropenia (65 [16%] in the bevacizumab and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%], respectively). Treatment-related deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group. Interpretation Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer. This approach is also being investigated in other tumour types, including metastatic breast and non-small cell lung cancers. Funding F Hoffmann-La Roche.read more
Citations
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Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer
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ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
E. Van Cutsem,Andrés Cervantes,René Adam,Alberto Sobrero,J.H.J.M. van Krieken,Dan Aderka,E. Aranda Aguilar,Alberto Bardelli,Al B. Benson,György Bodoky,Fortunato Ciardiello,André D'Hoore,Eduardo Díaz-Rubio,J.-Y. Douillard,Michel Ducreux,Alfredo Falcone,Axel Grothey,Thomas Gruenberger,Karin Haustermans,Volker Heinemann,Paulo M. Hoff,C.-H. Köhne,R. Labianca,Pierre Laurent-Puig,Brigette B.Y. Ma,Tim Maughan,Kei Muro,Nicola Normanno,Pia Österlund,Pia Österlund,Wim J.G. Oyen,Demetris Papamichael,George Pentheroudakis,Per Pfeiffer,Timothy J. Price,C.J.A. Punt,Jens Ricke,Arnaud Roth,R. Salazar,Werner Scheithauer,H.-J. Schmoll,Josep Tabernero,Julien Taieb,Sabine Tejpar,Harpreet Wasan,Takayuki Yoshino,Aziz Zaanan,Dirk Arnold +47 more
TL;DR: These ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
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Influence of tumour micro-environment heterogeneity on therapeutic response
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Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer
Toshiaki Watanabe,Michio Itabashi,Yasuhiro Shimada,Shinji Tanaka,Yoshinori Ito,Yoichi Ajioka,Tetsuya Hamaguchi,Ichinosuke Hyodo,Masahiro Igarashi,Hideyuki Ishida,Megumi Ishiguro,Yukihide Kanemitsu,Norihiro Kokudo,Kei Muro,Atsushi Ochiai,Masahiko Oguchi,Yasuo Ohkura,Yutaka Saito,Yoshiharu Sakai,Hideki Ueno,Takayuki Yoshino,Takahiro Fujimori,Nobuo Koinuma,Takayuki Morita,Genichi Nishimura,Yuh Sakata,Keiichi Takahashi,Hiroya Takiuchi,Osamu Tsuruta,Toshiharu Yamaguchi,Masahiro Yoshida,Naohiko Yamaguchi,Kenjiro Kotake,Kenichi Sugihara,Rectum +34 more
TL;DR: The English version of the JSCCR Guidelines 2016 is presented, which can be used as a tool for treating colorectal cancer in actual clinical practice settings and as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient.
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Clinical practice guidelines in oncology
William J. Gradishar,Benjamin O. Anderson,Ron Balassanian,Sarah L. Blair,Harold J. Burstein,Amy E. Cyr,Anthony D. Elias,William B. Farrar,Andres Forero,Sharon H. Giordano,Matthew P. Goetz,Lori J. Goldstein,Steven J. Isakoff,Janice A. Lyons,P. Kelly Marcom,Ingrid A. Mayer,Beryl McCormick,Meena S. Moran,Ruth O'Regan,Sameer A. Patel,Lori J. Pierce,Elizabeth C. Reed,Kilian E. Salerno,Lee S. Schwartzberg,Amy Sitapati,Karen L. Smith,Mary Lou Smith,Hatem Soliman,George Somlo,Melinda L. Telli,John H. Ward,Rashmi Kumar,Dorothy A. Shead +32 more
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
References
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Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
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Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer
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Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study
Leonard B. Saltz,Stephen Clarke,Eduardo Díaz-Rubio,Werner Scheithauer,Arie Figer,Ralph Wong,Sheryl Koski,Mikhail Lichinitser,T. Yang,Fernando Rivera,Félix Couture,Florin Sirzen,Jim Cassidy +12 more
TL;DR: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC.
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