SCOPE1
Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial
Phase 2/3N = 258NCT00509561
- Population
- Non-metastatic, histologically confirmed oesophageal carcinoma (adenocarcinoma, squamous-cell or undifferentiated), WHO performance status 0 to 1, stage I to III, selected for definitive chemoradiotherapy
- Design
- Multicentre, open-label, randomised (1:1) phase 2/3 trial in 36 UK centres. Definitive chemoradiotherapy: cisplatin 60 mg/m2 on day 1 and capecitabine 625 mg/m2 twice daily on days 1 to 21 for four cycles, with 50 Gy in 25 fractions during cycles three and four; experimental arm added cetuximab 400 mg/m2 then 250 mg/m2 weekly. Phase 2 primary endpoint: treatment-failure-free at week 24; phase 3 primary endpoint: overall survival. Recruitment (February 2008 to February 2012) stopped for futility before the phase 3 stage. ISRCTN registry number 47718479, also listed on ClinicalTrials.gov as NCT00509561 (registry enrolment 259, paper 258).
- Primary endpoint
- Treatment failure-free at 24 weeks, OS
- Arms
- Chemoradiotherapy (control, n = 129): Cisplatin and capecitabine, four cycles, with 50 Gy radiotherapy
- Chemoradiotherapy plus cetuximab (experimental, n = 129): Cisplatin and capecitabine with 50 Gy radiotherapy, plus cetuximab 400 mg/m2 then 250 mg/m2 weekly
- People
- Crosby T
Δ Treatment failure-free at 24 weeks−10.5 pointsOSHR 1.53 (95% CI 1.03–2.27)Δ median OS−3.3 months
Show the numbers
| Endpoint | Analysis | Chemoradiotherapy plus cetuximab | Chemoradiotherapy | Effect |
|---|---|---|---|---|
| Treatment failure-free at 24 weeksPatients evaluable for the 24-week endpoint (119 and 121) | primaryCrosby 2013 | 66.4% | 76.9% | Phase 2 primary endpoint. The abstract gives 90% confidence intervals (cetuximab group 58.6 to 73.6; chemoradiotherapy only 69.7 to 83.0), so no ci95 is entered. |
| OSIntention-to-treat (258 patients; 129 per group) | exploratorymedian follow-up 16.8 monthsCrosby 2013 | median 22.1 months (15.1–24.5) | median 25.4 months (20.5–37.9) | HR 1.53 (95% CI 1.03–2.27)P=0.035The phase 3 stage, whose primary endpoint was overall survival, was not reached because the trial stopped for futility; this comparison comes from the stopped trial. Hazard ratio is adjusted. Median follow-up of surviving patients 16.8 months. Non-haematological grade 3 or 4 toxicities: 79% (102 of 129) with cetuximab vs 63% (81 of 129). |
| Endpoint | Analysis | Chemoradiotherapy plus cetuximab | Chemoradiotherapy | Effect |
|---|---|---|---|---|
| Treatment failure-free at 24 weeksPatients evaluable for the 24-week endpoint (119 and 121) | primaryCrosby 2013 | 66.4% | 76.9% | Phase 2 primary endpoint. The abstract gives 90% confidence intervals (cetuximab group 58.6 to 73.6; chemoradiotherapy only 69.7 to 83.0), so no ci95 is entered. |
| OSIntention-to-treat (258 patients; 129 per group) | exploratorymedian follow-up 16.8 monthsCrosby 2013 | median 22.1 months (15.1–24.5) | median 25.4 months (20.5–37.9) | HR 1.53 (95% CI 1.03–2.27)P=0.035The phase 3 stage, whose primary endpoint was overall survival, was not reached because the trial stopped for futility; this comparison comes from the stopped trial. Hazard ratio is adjusted. Median follow-up of surviving patients 16.8 months. Non-haematological grade 3 or 4 toxicities: 79% (102 of 129) with cetuximab vs 63% (81 of 129). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 1.53 | 1.03–2.27 |
- Chemoradiotherapy plus cetuximab (experimental)
- Chemoradiotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Chemoradiotherapy plus cetuximab | Chemoradiotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 16 | 60.5% | 64.6% |
| 32 | 36.7% | 41.8% |
| 48 | 22.2% | 27.0% |
| 64 | 13.4% | 17.4% |