Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 303-312 |
| Number of pages | 10 |
| Journal | The Lancet |
| Volume | 381 |
| Issue number | 9863 |
| DOIs | |
| State | Published - Jan 2013 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT) : An international, multicentre, randomised, placebo-controlled, phase 3 trial. / Grothey, Axel F; Van Cutsem, Eric; Sobrero, Alberto; Siena, Salvatore; Falcone, Alfredo; Ychou, Marc; Humblet, Yves; Bouché, Olivier; Mineur, Laurent; Barone, Carlo; Adenis, Antoine; Tabernero, Josep; Yoshino, Takayuki; Lenz, Heinz Josef; Goldberg, Richard M.; Sargent, Daniel J.; Cihon, Frank; Cupit, Lisa; Wagner, Andrea; Laurent, Dirk.
In: The Lancet, Vol. 381, No. 9863, 01.2013, p. 303-312.Research output: Contribution to journal › Article
}
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 F
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84872921660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872921660&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(12)61900-X
DO - 10.1016/S0140-6736(12)61900-X
M3 - Article
VL - 381
SP - 303
EP - 312
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9863
ER -