Entry Detail
| General information | |
| Database: | DB00018 |
| Objective: | 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 internationalphase 3 trial was done to assess the multikinase inhibitor regorafenib in these patients. |
| Authors: | Grothey A, et al |
| Title: | Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebocontrolled, phase 3 trial. |
| Journal: | Lancet. |
| Year: | 2013 |
| PMID: | 23177514 |
| Trial Design | |
| Clinical Trial Id: | NCT01103323 |
| Agent: | regorafenib |
| Target: | Protooncogene tyrosineprotein kinase receptor ret Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Vascular endothelial growth factor receptor 3 |
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an international, multicentre, randomised, placebocontrolled, phase III trial. |
| Key Patients Feature: | Patients with documented metastatic colorectal cancer and progression during or within 3 months after the last standard therapy were randomised |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | best supportive care+ placebo |
| Treatment Info: | Pts were randomized in a 2:1 ratio; by computergenerated randomisation list and interactive voice response system; preallocated block design (block size six); stratified by previous treatment with VEGFtargeting 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. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 753 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | No patients had a complete response; five patients assigned regorafenib and one patient assigned placebo had a partial response, giving objective response rates of 1.0% and 0.4%, respectively (p=0.19) |
| Disease Control Rate: | Disease control (partial response plus stable disease assessed at least 6 weeks after randomisation) was achieved in 207 (41%) of 505 patients assigned regorafenib and 38 (15%) patients assigned placebo (p<0.0001). Median duration of stable disease was 2.0 months (IQR 1.7-4.0) in the regorafenib group and 1.7 months (1.4-1.9) in the placebo group. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | all subgroup analyses significantly favoured regorafenib compared with placebo, except for patients from eastern Europe, for whom the difference was not significant |
| Median OS A vs. C: | 6.4 months in the regorafenib group versus 5.0 months in the placebo group (hazard ratio 0.77; 95% CI 0.640.94; onesided p=0.0052). |
| Adverse Event(agent arm): | Treatmentrelated 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 handfoot skin reaction (83 patients, 17%), fatigue (48, 10%), diarrhoea (36, 7%), hypertension (36, 7%), and rash or desquamation (29, 6%). |
| Conclusions: | Regorafenib is the first smallmolecule 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 treatmentrefractory population. |