CO.17
A Phase III Randomized Study of Cetuximab (Erbitux™, C225) and Best Supportive Care Versus Best Supportive Care in Patients With Pretreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Positive Colorectal Carcinoma
Phase 3N = 572NCT00079066
- Population
- Colorectal cancer with immunohistochemically detectable EGFR, previously treated with a fluoropyrimidine, irinotecan and oxaliplatin or with contraindications to these drugs
- Design
- Randomised trial, December 2003 to August 2005: cetuximab (initial dose 400 mg per square metre, then 250 mg per square metre weekly) plus best supportive care versus best supportive care alone. A later analysis tested tumour samples for activating mutations in exon 2 of K-ras.
- Primary endpoint
- OS
- Arms
- Cetuximab plus BSC (experimental, n = 287): Cetuximab 400 mg per square metre initially, then 250 mg per square metre weekly, plus best supportive care
- Best supportive care (control, n = 285): Best supportive care alone
- People
- Jonker DJ
OSHR 0.77 (95% CI 0.64–0.92)Δ median OS+1.5 monthsPFSHR 0.68 (95% CI 0.57–0.80)OSHR 0.55 (95% CI 0.41–0.74)Δ median OS+4.7 monthsPFSHR 0.40 (95% CI 0.30–0.54)
Show the numbers
| Endpoint | Analysis | Cetuximab plus BSC | Best supportive care | Effect |
|---|---|---|---|---|
| OSAll randomised patients (analysis population not stated in the abstract) | primaryJonker 2007 | median 6.1 months | median 4.6 months | HR 0.77 (95% CI 0.64–0.92)P=0.005 |
| PFSAll randomised patients (analysis population not stated in the abstract) | primaryJonker 2007 | — | — | HR 0.68 (95% CI 0.57–0.80)P<0.001Hazard ratio for disease progression or death; medians not given in the abstract. |
| ORRAll randomised patients (analysis population not stated in the abstract) | primaryJonker 2007 | 8% | — | P<0.001Partial responses in 23 patients (8.0%) with cetuximab; none (0%) with supportive care alone. |
| OSPatients with wild-type K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | median 9.5 months | median 4.8 months | HR 0.55 (95% CI 0.41–0.74)P<0.001Biomarker analysis; tumour samples were available for 394 of 572 patients (68.9%) and 42.3% of those tested had at least one exon 2 mutation. The interaction of K-ras status with overall survival had P=0.01. |
| PFSPatients with wild-type K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | median 3.7 months | median 1.9 months | HR 0.40 (95% CI 0.30–0.54)P<0.001Hazard ratio for progression or death. The interaction of K-ras status with progression-free survival had P<0.001. |
| OSPatients with mutated K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | — | — | HR 0.98P=0.89No significant difference between cetuximab plus supportive care and supportive care alone; confidence interval not given in the abstract. |
| PFSPatients with mutated K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | — | — | HR 0.99P=0.96Hazard ratio for progression or death; confidence interval not given in the abstract. |
| Endpoint | Analysis | Cetuximab plus BSC | Best supportive care | Effect |
|---|---|---|---|---|
| OSAll randomised patients (analysis population not stated in the abstract) | primaryJonker 2007 | median 6.1 months | median 4.6 months | HR 0.77 (95% CI 0.64–0.92)P=0.005 |
| PFSAll randomised patients (analysis population not stated in the abstract) | primaryJonker 2007 | — | — | HR 0.68 (95% CI 0.57–0.80)P<0.001Hazard ratio for disease progression or death; medians not given in the abstract. |
| ORRAll randomised patients (analysis population not stated in the abstract) | primaryJonker 2007 | 8% | — | P<0.001Partial responses in 23 patients (8.0%) with cetuximab; none (0%) with supportive care alone. |
| OSPatients with wild-type K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | median 9.5 months | median 4.8 months | HR 0.55 (95% CI 0.41–0.74)P<0.001Biomarker analysis; tumour samples were available for 394 of 572 patients (68.9%) and 42.3% of those tested had at least one exon 2 mutation. The interaction of K-ras status with overall survival had P=0.01. |
| PFSPatients with wild-type K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | median 3.7 months | median 1.9 months | HR 0.40 (95% CI 0.30–0.54)P<0.001Hazard ratio for progression or death. The interaction of K-ras status with progression-free survival had P<0.001. |
| OSPatients with mutated K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | — | — | HR 0.98P=0.89No significant difference between cetuximab plus supportive care and supportive care alone; confidence interval not given in the abstract. |
| PFSPatients with mutated K-ras tumours (exon 2) among 394 of 572 tested | exploratoryKarapetis 2008 | — | — | HR 0.99P=0.96Hazard ratio for progression or death; confidence interval not given in the abstract. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.77 | 0.64–0.92 |
| PFS | 0.68 | 0.57–0.8 |
| OS | 0.55 | 0.41–0.74 |
| PFS | 0.4 | 0.3–0.54 |
- Best supportive care (control)
- Cetuximab plus BSC (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Best supportive care | Cetuximab plus BSC |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 4 | 54.7% | 63.5% |
| 8 | 30.0% | 40.3% |
| 11 | 19.1% | 28.7% |
| 15 | 10.4% | 18.2% |
- Best supportive care (control)
- Cetuximab plus BSC (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Best supportive care | Cetuximab plus BSC |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 42.0% | 64.5% |
| 12 | 17.7% | 41.7% |
| 18 | 7.4% | 26.9% |
| 24 | 3.1% | 17.4% |
Appears in
Sources
Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357(20):2040-8.
Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359(17):1757-65.