New EPOC
Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial
Phase 3N = 257NCT00482222
- Population
- KRAS wild-type resectable or suboptimally resectable colorectal liver metastases
- Design
- Multicentre, open-label randomised phase 3 trial (registered ISRCTN22944367) in patients with KRAS exon 2 wild-type resectable or suboptimally resectable colorectal liver metastases (the 2020 report states KRAS codons 12, 13 and 61 wild-type, WHO performance status 0 to 2): chemotherapy (oxaliplatin with infusional fluorouracil, or oxaliplatin with oral capecitabine; irinotecan with fluorouracil allowed after adjuvant oxaliplatin) with or without cetuximab, before and after liver resection, randomised 1:1. The primary endpoint was progression-free survival. Recruitment was halted on 1 November 2012 on the advice of the Trial Steering Committee (the 2014 report: protocol-defined futility criteria met). 272 patients were randomly assigned between February 2007 and October 2012; the primary analysis population of 257 KRAS wild-type patients (128 chemotherapy alone, 129 with cetuximab) excludes one patient assigned in error and 14 randomised before the KRAS amendment who were retrospectively found KRAS-mutant or indeterminate (2020 report).
- Primary endpoint
- PFS
- Arms
- Chemotherapy alone (control, n = 128): Oxaliplatin-based chemotherapy (or irinotecan with fluorouracil after adjuvant oxaliplatin) before and after liver resection
- Chemotherapy plus cetuximab (experimental, n = 129): The same chemotherapy plus cetuximab before and after liver resection
- People
- Primrose J
PFSHR 1.48 (95% CI 1.04–2.12)Δ median PFS−6.4 monthsPFSHR 1.17 (95% CI 0.87–1.56)Δ median PFS−6.7 monthsOSHR 1.45 (95% CI 1.02–2.05)Δ median OS−25.6 months
Show the numbers
| Endpoint | Analysis | Chemotherapy plus cetuximab | Chemotherapy alone | Effect |
|---|---|---|---|---|
| PFSPatients included in the primary analysis (117 with chemotherapy alone; 119 with chemotherapy plus cetuximab) | interimmedian follow-up 20.7 monthsPrimrose 2014 | median 14.1 months (11.8–15.9) | median 20.5 months (16.8–26.7) | HR 1.48 (95% CI 1.04–2.12)P=0.030Interim analysis up to 1 November 2012, when the trial closed. A hazard ratio above 1 means shorter progression-free survival with cetuximab. |
| PFSPrimary analysis population (intention-to-treat population with known KRAS codon 12, 13 and 61 wild-type status; n=257) | long term-updatemedian follow-up 66.7 monthsBridgewater 2020 | median 15.5 months (13.8–19.0) | median 22.2 months (18.3–26.8) | HR 1.17 (95% CI 0.87–1.56)P=0.304Analysis 5 years after the last patient was recruited. The abstract states that progression-free survival was the primary endpoint published previously. Hazard ratio above 1 means shorter progression-free survival with cetuximab (direction taken from the medians; the full text words it as 'chemotherapy without versus with cetuximab'). |
| OSPrimary analysis population (intention-to-treat population with known KRAS codon 12, 13 and 61 wild-type status; n=257) | long term-updatemedian follow-up 66.7 monthsBridgewater 2020 | median 55.4 months (43.5–71.5) | median 81 months | HR 1.45 (95% CI 1.02–2.05)P=0.036Secondary endpoint. The abstract gives the confidence interval for the chemotherapy-alone median as 59.6 months to not reached, so it is not recorded as a numeric interval. Hazard ratio above 1 means shorter overall survival with cetuximab (direction taken from the medians). |
| Endpoint | Analysis | Chemotherapy plus cetuximab | Chemotherapy alone | Effect |
|---|---|---|---|---|
| PFSPatients included in the primary analysis (117 with chemotherapy alone; 119 with chemotherapy plus cetuximab) | interimmedian follow-up 20.7 monthsPrimrose 2014 | median 14.1 months (11.8–15.9) | median 20.5 months (16.8–26.7) | HR 1.48 (95% CI 1.04–2.12)P=0.030Interim analysis up to 1 November 2012, when the trial closed. A hazard ratio above 1 means shorter progression-free survival with cetuximab. |
| PFSPrimary analysis population (intention-to-treat population with known KRAS codon 12, 13 and 61 wild-type status; n=257) | long term-updatemedian follow-up 66.7 monthsBridgewater 2020 | median 15.5 months (13.8–19.0) | median 22.2 months (18.3–26.8) | HR 1.17 (95% CI 0.87–1.56)P=0.304Analysis 5 years after the last patient was recruited. The abstract states that progression-free survival was the primary endpoint published previously. Hazard ratio above 1 means shorter progression-free survival with cetuximab (direction taken from the medians; the full text words it as 'chemotherapy without versus with cetuximab'). |
| OSPrimary analysis population (intention-to-treat population with known KRAS codon 12, 13 and 61 wild-type status; n=257) | long term-updatemedian follow-up 66.7 monthsBridgewater 2020 | median 55.4 months (43.5–71.5) | median 81 months | HR 1.45 (95% CI 1.02–2.05)P=0.036Secondary endpoint. The abstract gives the confidence interval for the chemotherapy-alone median as 59.6 months to not reached, so it is not recorded as a numeric interval. Hazard ratio above 1 means shorter overall survival with cetuximab (direction taken from the medians). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 1.48 | 1.04–2.12 |
| PFS | 1.17 | 0.87–1.56 |
| OS | 1.45 | 1.02–2.05 |
- Chemotherapy plus cetuximab (experimental)
- Chemotherapy alone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Chemotherapy plus cetuximab | Chemotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 13 | 52.8% | 64.4% |
| 26 | 27.9% | 41.5% |
| 38 | 15.4% | 27.7% |
| 51 | 8.2% | 17.8% |
- Chemotherapy plus cetuximab (experimental)
- Chemotherapy alone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Chemotherapy plus cetuximab | Chemotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 53.5% | 64.6% |
| 28 | 28.6% | 41.7% |
| 42 | 15.3% | 26.9% |
| 56 | 8.2% | 17.4% |
Appears in
Sources
Primrose J, Falk S, Finch-Jones M, Valle J, O'Reilly D, Siriwardena A, et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol. 2014;15(6):601-11.
Bridgewater JA, Pugh SA, Maishman T, Eminton Z, Mellor J, Whitehead A, et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020;21(3):398-411.