ESPAC-1
Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer (European Study Group for Pancreatic Cancer 1 trial)
N = 541
- Population
- Eligible patients with resected pancreatic ductal adenocarcinoma: 541 randomised, of whom 285 entered the factorial design in the 2001 report (289 in the 2004 report); the others were randomised to one main comparison only.
- Design
- Multicentre randomised trial after resection. Patients could enter a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or one of two main comparisons (chemoradiotherapy versus none, or chemotherapy versus none). Chemoradiotherapy: 20 Gy in ten daily fractions over 2 weeks with fluorouracil 500 mg/m2 on days 1-3, repeated after 2 weeks. Chemotherapy: fluorouracil 425 mg/m2 plus folinic acid 20 mg/m2 daily for 5 days, monthly for 6 months. Primary endpoint death; all analyses by intention to treat (2001 abstract). The four arms below are the marginal comparisons of the 2001 report and overlap, because patients in the factorial design contribute to two of them. The 2004 report analysed 289 patients in the factorial design (73 chemoradiotherapy alone, 75 chemotherapy alone, 72 both, 69 observation). No registry accession number appears in either PubMed record.
- Primary endpoint
- OS
- Arms
- With adjuvant chemotherapy (experimental, n = 238): Fluorouracil plus folinic acid, monthly for 6 months (alone or with chemoradiotherapy)
- Without adjuvant chemotherapy (control, n = 235): No chemotherapy (observation or chemoradiotherapy alone)
- With adjuvant chemoradiotherapy (experimental, n = 175): 20 Gy in ten fractions with fluorouracil (alone or with chemotherapy)
- Without adjuvant chemoradiotherapy (control, n = 178): No chemoradiotherapy (observation or chemotherapy alone)
- People
- Neoptolemos JP, European Study Group for Pancreatic Cancer
OSHR 0.66 (95% CI 0.52–0.83)Δ median OS+5.7 monthsOSHR 1.18 (95% CI 0.90–1.55)Δ median OS−0.6 monthsΔ 60-month OS+13 pointsΔ 60-month OS−10 points
Show the numbers
| Endpoint | Analysis | With adjuvant chemotherapy / With adjuvant chemoradiotherapy | Without adjuvant chemotherapy / Without adjuvant chemoradiotherapy | Effect |
|---|---|---|---|---|
| OS | interimmedian follow-up 10 monthsNeoptolemos 2001 | median 19.7 months | median 14 months | HR 0.66 (95% CI 0.52–0.83)P=0.0005Chemotherapy versus no chemotherapy, pooled over the factorial and single-comparison patients (238 versus 235). The 2004 paper describes its own report as the final results and an update of this interim analysis. The 2001 median follow-up of 10 months is that of the 227 patients (42%) still alive. |
| OS | interimmedian follow-up 10 monthsNeoptolemos 2001 | median 15.5 months | median 16.1 months | HR 1.18 (95% CI 0.90–1.55)P=0.24Chemoradiotherapy versus no chemoradiotherapy (175 versus 178); the authors report no benefit. |
| OSPatients in the two-by-two factorial design (289); analysis population not labelled in the abstract | finalmedian follow-up 47 monthsNeoptolemos 2004 | 21% at 5 y | 8% at 5 y | P=0.009Estimated five-year survival rate among patients who did and did not receive chemotherapy in the factorial analysis; the abstract gives no confidence intervals or hazard ratio for this comparison. Arm sizes here are those of the 2001 report; the 2004 analysis used the 289 factorial patients. |
| OSPatients in the two-by-two factorial design (289); analysis population not labelled in the abstract | finalmedian follow-up 47 monthsNeoptolemos 2004 | 10% at 5 y | 20% at 5 y | P=0.05Estimated five-year survival rate among patients who did and did not receive chemoradiotherapy in the factorial analysis; the abstract gives no confidence intervals or hazard ratio. The authors describe the effect of chemoradiotherapy on survival as deleterious. |
| Endpoint | Analysis | With adjuvant chemotherapy / With adjuvant chemoradiotherapy | Without adjuvant chemotherapy / Without adjuvant chemoradiotherapy | Effect |
|---|---|---|---|---|
| OS | interimmedian follow-up 10 monthsNeoptolemos 2001 | median 19.7 months | median 14 months | HR 0.66 (95% CI 0.52–0.83)P=0.0005Chemotherapy versus no chemotherapy, pooled over the factorial and single-comparison patients (238 versus 235). The 2004 paper describes its own report as the final results and an update of this interim analysis. The 2001 median follow-up of 10 months is that of the 227 patients (42%) still alive. |
| OS | interimmedian follow-up 10 monthsNeoptolemos 2001 | median 15.5 months | median 16.1 months | HR 1.18 (95% CI 0.90–1.55)P=0.24Chemoradiotherapy versus no chemoradiotherapy (175 versus 178); the authors report no benefit. |
| OSPatients in the two-by-two factorial design (289); analysis population not labelled in the abstract | finalmedian follow-up 47 monthsNeoptolemos 2004 | 21% at 5 y | 8% at 5 y | P=0.009Estimated five-year survival rate among patients who did and did not receive chemotherapy in the factorial analysis; the abstract gives no confidence intervals or hazard ratio for this comparison. Arm sizes here are those of the 2001 report; the 2004 analysis used the 289 factorial patients. |
| OSPatients in the two-by-two factorial design (289); analysis population not labelled in the abstract | finalmedian follow-up 47 monthsNeoptolemos 2004 | 10% at 5 y | 20% at 5 y | P=0.05Estimated five-year survival rate among patients who did and did not receive chemoradiotherapy in the factorial analysis; the abstract gives no confidence intervals or hazard ratio. The authors describe the effect of chemoradiotherapy on survival as deleterious. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.66 | 0.52–0.83 |
| OS | 1.18 | 0.9–1.55 |
- With adjuvant chemotherapy (experimental)
- Without adjuvant chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | With adjuvant chemotherapy | Without adjuvant chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 12 | 65.6% | 55.2% |
| 25 | 41.5% | 29.0% |
| 37 | 27.2% | 16.0% |
| 49 | 17.8% | 8.8% |
- With adjuvant chemoradiotherapy (experimental)
- Without adjuvant chemoradiotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | With adjuvant chemoradiotherapy | Without adjuvant chemoradiotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 63.9% | 65.0% |
| 20 | 40.9% | 42.3% |
| 30 | 26.1% | 27.5% |
| 40 | 16.7% | 17.9% |
Appears in
Sources
Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358(9293):1576-85.
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200-10.