Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT)

An international, multicentre, randomised, placebo-controlled, phase 3 trial

Axel F 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

Research output: Contribution to journalArticle

1223 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)303-312
Number of pages10
JournalThe Lancet
Volume381
Issue number9863
DOIs
StatePublished - Jan 2013

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Colorectal Neoplasms
Placebos
Therapeutics
Survival
regorafenib
Intention to Treat Analysis
Drug Delivery Systems
Random Allocation
Exanthema
Vascular Endothelial Growth Factor A
Population
Fatigue
Disease Progression
Foot
Diarrhea
Hand
Research Personnel
Hypertension
Delivery of Health Care
Safety

ASJC Scopus subject areas

  • Medicine(all)

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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 journalArticle

Grothey, AF, Van Cutsem, E, Sobrero, A, Siena, S, Falcone, A, Ychou, M, Humblet, Y, Bouché, O, Mineur, L, Barone, C, Adenis, A, Tabernero, J, Yoshino, T, Lenz, HJ, Goldberg, RM, Sargent, DJ, Cihon, F, Cupit, L, Wagner, A & Laurent, D 2013, 'Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial', The Lancet, vol. 381, no. 9863, pp. 303-312. https://doi.org/10.1016/S0140-6736(12)61900-X
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. / Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT) : An international, multicentre, randomised, placebo-controlled, phase 3 trial. In: The Lancet. 2013 ; Vol. 381, No. 9863. pp. 303-312.
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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.

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