| General information |
| Database: | DB00025 |
| Objective: | In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)targeted antibody cetuximab was added to standard chemotherapy in firstline treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. |
| Authors: | Maughan TS, et al |
| Title: | Addition of cetuximab to oxaliplatinbased firstline combination chemotherapy for treatment of advanced colorectal cancer: results of the randomisedphase 3 MRC COIN trial. |
| Journal: | Lancet |
| Year: | 2011 |
| PMID: | 21641636 |
| Trial Design |
| Clinical Trial Id: | ISRCTN27286448 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | cetuximab+ oxaliplatinbased |
| Study Type: | a randomisedphase III MRC COIN trial |
| Key Patients Feature: | patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer |
| Biomarker: | somatic mutation status: BRAF mutant; KRAS mutant; all wildtype. |
| Biomark Analysis: | Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8.8 months (IQR 4.527.4); KRAS mutant, 14.4 months (8.524.0); all wildtype, 20.1 months (11.531.7). |
| Control Group Info: | oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C) |
| Treatment Info: | patients were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. |
| Primary End Point: | overall survival in patients with KRAS wildtype tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. |
| Secondary End Point: | NA |
| Patients Number: | 1630 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0.049). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | There was no effect on progression free survival (8.6 months [IQR 5.012.5] in the control group vs 8.6 months [5.113.8] in the cetuximab group; HR 0.96, 0.821.12, p=0.60). |
| Median OS A vs. C: | In patients with KRAS wildtype tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17.9 months [IQR 10.329.2] in the control group vs 17.0 months [9.430.1] in the cetuximab group; HR 1.04, 95% CI 0.871.23, p=0.67). |
| Adverse Event(agent arm): | Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wildtype tumours, respectively). |
| Conclusions: | This trial has not confirmed a benefit of addition of cetuximab to oxaliplatinbased chemotherapy in firstline treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression free or overall survival in KRAS wildtype patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in firstline chemotherapy in patients with widespread metastases cannot be recommended. |