TY - JOUR
T1 - Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT)
T2 - An international, multicentre, randomised, placebo-controlled, phase 3 trial
AU - Grothey, Axel
AU - Van Cutsem, Eric
AU - Sobrero, Alberto
AU - Siena, Salvatore
AU - Falcone, Alfredo
AU - Ychou, Marc
AU - Humblet, Yves
AU - Bouché, Olivier
AU - Mineur, Laurent
AU - Barone, Carlo
AU - Adenis, Antoine
AU - Tabernero, Josep
AU - Yoshino, Takayuki
AU - Lenz, Heinz Josef
AU - Goldberg, Richard M.
AU - Sargent, Daniel J.
AU - Cihon, Frank
AU - Cupit, Lisa
AU - Wagner, Andrea
AU - Laurent, Dirk
N1 - Funding Information:
The Mayo Foundation has received research funding for clinical studies done by AG from Genentech, Sanofi, Bayer, Daiichi, and Imclone and has received honoraria for consulting activities of AG for Genentech, Roche, Onyx, Bayer, Imclone, Bristol-Myers Squibb, and Sanofi. EVC has received research funding from Bayer. AS has been an advisory board member and has spoken at symposia for Roche, Merck, Bayer, Amgen, and Sanofi. SS has been an advisory board member for Amgen, AstraZeneca, Bayer, Genentech, Merck Serono, Roche, and Sanofi. AF has received honoraria from Amgen, Bayer, Merck Serono, Roche, and Sanofi for speaking, consultancy, and advisory board membership, and has received research support from Amgen, Bayer, Merck Serono, Roche, and Sanofi. MY has received honoraria from Bayer for advisory board membership. YH has received honoraria from Bayer to act as a consultant and has received research funding from Bayer. OB has received honoraria from Roche, Merck Serono, and Amgen. LM declares that he has no conflicts of interest. CB has received honoraria for lecturing and advisory board membership from Bayer, Merck, Roche, and Novartis, and has received honoraria for lecturing from GlaxoSmithKline and Amgen. AA has received honoraria from Bayer (conference and research funding). JT has been a consultant and advisory board member for Amgen, Bristol-Myers Squibb, Genentech, Merck KGaA, Millennium, Novartis, Onyx, Pfizer, Roche, Sanofi, and Bayer and has received honoraria from Amgen, Merck KGaA, Novartis, Roche, and Sanofi. TY has received consulting fees from Takeda, honoraria from Chugai, Takeda, Yakult, Bristol-Myers Squibb, and Merck Serono, and research funding from Daiichi Sankyo, Taiho, Bayer, and Imclone. H-JL has been an advisory board member for Bayer. RMG has received research support to Ohio State University from Sanofi, Bayer, Myriad, and Jennerex, has provided unpaid consultancy for Bayer and Sanofi, and has received payment from Lilly for participation in a data safety monitoring board. DJS has received consulting fees from the CORRECT steering committee (less than $5000/year). FC, LC, AW, and DL are employees of Bayer. FC and DL have Bayer stock ownership.
Funding Information:
We thank the participating patients and staff at each of the study centres. The trial was supported by Bayer HealthCare Pharmaceuticals. Editorial assistance in the preparation of this manuscript was provided by Succinct Healthcare Communications, with financial support from Bayer HealthCare Pharmaceuticals; the authors retained editorial control over the content.
PY - 2013/1
Y1 - 2013/1
N2 - 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 computergenerated randomisation list and interactive voice response system; preallocated block design (block size six); stratifi ed 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 fi rst 3 week s of each 4 week cycle. The primary endpoint was overall survival. The study sponsor, participants, and investigators were masked to treatment assignment. Effi cacy 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 fi rst small-molecule multikinase inhibitor with survival benefi ts 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 off ering a potential new line of therapy in this treatment-refractory population. Funding Bayer HealthCare Pharmaceuticals.
AB - 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 computergenerated randomisation list and interactive voice response system; preallocated block design (block size six); stratifi ed 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 fi rst 3 week s of each 4 week cycle. The primary endpoint was overall survival. The study sponsor, participants, and investigators were masked to treatment assignment. Effi cacy 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 fi rst small-molecule multikinase inhibitor with survival benefi ts 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 off ering a potential new line of therapy in this treatment-refractory population. Funding Bayer HealthCare Pharmaceuticals.
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U2 - 10.1016/S0140-6736(12)61900-X
DO - 10.1016/S0140-6736(12)61900-X
M3 - Article
C2 - 23177514
AN - SCOPUS:84872921660
VL - 381
SP - 303
EP - 312
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9863
ER -