Document Detail


Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial.
MedLine Citation:
PMID:  23177514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: No treatment options are available for patients with metastatic colorectal cancer that progresses after all approved standard therapies, but many patients maintain a good performance status and could be candidates for further therapy. An international phase 3 trial was done to assess the multikinase inhibitor regorafenib in these patients.
METHODS: We did this trial at 114 centres in 16 countries. Patients with documented metastatic colorectal cancer and progression during or within 3 months after the last standard therapy were randomised (in a 2:1 ratio; by computer-generated randomisation list and interactive voice response system; preallocated block design (block size six); stratified by previous treatment with VEGF-targeting drugs, time from diagnosis of metastatic disease, and geographical region) to receive best supportive care plus oral regorafenib 160 mg or placebo once daily, for the first 3 weeks of each 4 week cycle. The primary endpoint was overall survival. The study sponsor, participants, and investigators were masked to treatment assignment. Efficacy analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01103323.
FINDINGS: Between April 30, 2010, and March 22, 2011, 1052 patients were screened, 760 patients were randomised to receive regorafenib (n=505) or placebo (n=255), and 753 patients initiated treatment (regorafenib n=500; placebo n=253; population for safety analyses). The primary endpoint of overall survival was met at a preplanned interim analysis; data cutoff was on July 21, 2011. Median overall survival was 6·4 months in the regorafenib group versus 5·0 months in the placebo group (hazard ratio 0·77; 95% CI 0·64-0·94; one-sided p=0·0052). Treatment-related adverse events occurred in 465 (93%) patients assigned regorafenib and in 154 (61%) of those assigned placebo. The most common adverse events of grade three or higher related to regorafenib were hand-foot skin reaction (83 patients, 17%), fatigue (48, 10%), diarrhoea (36, 7%), hypertension (36, 7%), and rash or desquamation (29, 6%).
INTERPRETATION: Regorafenib is the first small-molecule multikinase inhibitor with survival benefits in metastatic colorectal cancer which has progressed after all standard therapies. The present study provides evidence for a continuing role of targeted treatment after disease progression, with regorafenib offering a potential new line of therapy in this treatment-refractory population.
FUNDING: Bayer HealthCare Pharmaceuticals.
Authors:
Axel Grothey; Eric Van Cutsem; Alberto Sobrero; Salvatore Siena; Alfredo Falcone; Marc Ychou; Yves Humblet; Olivier Bouché; Laurent Mineur; Carlo Barone; Antoine Adenis; Josep Tabernero; Takayuki Yoshino; Heinz-Josef Lenz; Richard M Goldberg; Daniel J Sargent; Frank Cihon; Lisa Cupit; Andrea Wagner; Dirk Laurent;
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Publication Detail:
Type:  Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-11-22
Journal Detail:
Title:  Lancet     Volume:  381     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-02-07     Revised Date:  2013-05-06    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  303-12     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 Elsevier Ltd. All rights reserved.
Affiliation:
Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01103323
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MeSH Terms
Descriptor/Qualifier:
Aged
Antineoplastic Agents / therapeutic use*
Colorectal Neoplasms / drug therapy,  mortality,  pathology*
Disease-Free Survival
Double-Blind Method
Female
Humans
Male
Middle Aged
Neoplasm Metastasis / drug therapy
Phenylurea Compounds / therapeutic use*
Protein Kinase Inhibitors / therapeutic use*
Pyridines / therapeutic use*
Survival Rate
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Phenylurea Compounds; 0/Protein Kinase Inhibitors; 0/Pyridines; 24T2A1DOYB/regorafenib
Investigator
Investigator/Affiliation:
Philip Beale / ; Kathryn Field / ; Peter Gibbs / ; Nick Pavlakis / ; Timothy Price / ; Eric Van Cutsem / ; Hans Prenen / ; Jochen Decaestecker / ; Alain Hendlisz / ; Yves Humblet / ; Marc Peeters / ; Jean-Luc Van Laethem / ; Mary Mackenzie / ; Wilson Miller / ; Mark Rother / ; Rafal Wierzbicki / ; Asif Shaik / ; Scott Berry / ; Jianming Xu / ; Vladimira Stahalova / ; Ilona Kocakova / ; Bohuslav Melichar / ; Eugen Kubala / ; Marc Ychou / ; Olivier Bouché / ; Thierry Andre / ; Antoine Adenis / ; Mohamed Hebbar / ; Olivier Dupuis / ; Jean-François Seitz / ; Laurent Mineur / ; Christian Borel / ; Hans-Joachim Schmoll / ; Martin Becker / ; Claudio Denzlinger / ; Volker Heinemann / ; Meinolf Karthaus / ; Claus-Henning Koehne / ; Nicolas Ziegenhagen / ; Hendrik Kroening / ; Wolfgang Schepp / ; Tanja Trarbach / ; Michael Clemens / ; Gunnar Folprecht / ; Ulrich Hacker / ; Ralf-Dieter Hofheinz / ; Arndt Vogel / ; Janos Szanto / ; Laszlo Thurzo / ; Adi Shani / ; Eina Shaham-Shmueli / ; Alex Beny / ; Ayala Hubert / ; Sofia Man / ; Baruch Brenner / ; Alberto Sobrero / ; Giacomo Carteni / ; Gabriele Luppi / ; Alfredo Falcone / ; Salvatore Siena / ; Alberto Zaniboni / ; Carlo Barone / ; Fortunato Ciardiello / ; Corrado Boni / ; Hideo Baba / ; Eishi Baba / ; Tadamichi Denda / ; Hirofumi Fujii / ; Junji Furuse / ; Etsuko Warita / ; Yoshito Komatsu / ; Nobuyuki Mizunuma / ; Tomohiro Nishina / ; Yasutsuna Sasaki / ; Hiroya Takiuchi / ; Wataru Okamoto / ; Kazuma Kobayashi / ; Hiroyuki Uetake / ; Takashi Ura / ; Yasuhide Yamada / ; Kensei Yamaguchi / ; Kentaro Yamazaki / ; Takayuki Yoshino / ; Hideyuki Mishima / ; A J Gelderblom / ; D H Verheul / ; Josep Tabernero / ; Rocio Garcia-Carbonero / ; Carles Pericay Pijaume / ; Cristina Gravalos / ; Manuel Benavides / ; Javier Sastre / ; Jaime Feliu / ; Mercedes Martinez Villaca / ; Arnaud Roth / ; Mustafa Benekli / ; Faruk Aykan / ; Axel Grothey / ; Billy Clowney / ; Martin Hyzinski / ; Ali Khojasteh / ; Marc Saltzman / ; Heinz-Josef Lenz / ; Udit Verma / ; John Kugler / ; Jyotsna Fuloria / ; Kenneth Nahum / ; George Kim / ; Rex Mowat / ; Philip Stella / ; Martin Wiesenfeld / ; Brian Dicarlo / ; George Geils / ; Youram Nassir /
Comments/Corrections
Comment In:
Lancet. 2013 May 4;381(9877):1538-9   [PMID:  23642697 ]
Lancet. 2013 May 4;381(9877):1537-8   [PMID:  23642695 ]
Lancet. 2013 Jan 26;381(9863):273-5   [PMID:  23177516 ]
Lancet. 2013 May 4;381(9877):1536-7   [PMID:  23642693 ]
Lancet. 2013 May 4;381(9877):1537   [PMID:  23642696 ]
Nat Rev Gastroenterol Hepatol. 2013 Jan;10(1):1   [PMID:  23229325 ]
Nat Rev Clin Oncol. 2013 Jan;10(1):1   [PMID:  23229184 ]

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