ACCORD 12/0405-Prodige 2
Randomized phase III trial comparing in a preoperative schedule the result of two concurrent chemoradiation schemes (45 Gy + capecitabine vs 50 Gy + capecitabine-oxaliplatin) on the rate of sterilization of the operative specimen in resectable rectal carcinomas T3-4 N0-2 M0
Phase 3N = 598NCT00227747
- Population
- Patients with rectal adenocarcinoma accessible to digital examination, staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum)
- Design
- Randomised phase 3 trial of 5 weeks of preoperative chemoradiotherapy in T3-4 Nx M0 rectal cancer (or T2 Nx distal anterior rectum). Cap 45: radiotherapy 45 Gy in 25 fractions with concurrent capecitabine 800 mg/m2 twice daily on 5 days per week. Capox 50: radiotherapy 50 Gy in 25 fractions with the same capecitabine and oxaliplatin 50 mg/m2 once weekly. 598 patients were randomised (299 and 299) between November 2005 and July 2008; total mesorectal excision was planned 6 weeks after chemoradiotherapy.
- Primary endpoint
- pCR
- Arms
- Cap 45 (control, n = 299): Radiotherapy 45 Gy in 25 fractions with concurrent capecitabine 800 mg/m2 twice daily, 5 days per week, for 5 weeks
- Capox 50 (experimental, n = 299): Radiotherapy 50 Gy in 25 fractions with concurrent capecitabine 800 mg/m2 twice daily, 5 days per week, and oxaliplatin 50 mg/m2 once weekly, for 5 weeks
- People
- Gérard JP
Δ pCR+5.3 pointsΔ Grade 3-4 acute toxicity+24 pointsΔ 36-month Local recurrence−1.7 pointsΔ 36-month OS+0.7 pointsΔ 36-month DFS+4.8 pointsDFSHR 1.02 (95% CI 0.76–1.36)
Show the numbers
| Endpoint | Analysis | Capox 50 | Cap 45 | Effect |
|---|---|---|---|---|
| pCRRandomly assigned patients (598); analysis population not stated in the abstractComplete sterilization of the operative specimen (ypCR), the primary end point | primaryGérard 2010 | 19.2% | 13.9% | P=0.09When ypCR was combined with 'few residual cells', the rate was 28.9% with Cap 45 and 39.4% with Capox 50 (P=0.008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P=0.02). Surgery was performed in 98% of patients in both groups. |
| Grade 3-4 acute toxicityRandomly assigned patients (598); analysis population not stated in the abstractPreoperative grade 3 to 4 toxicity | primaryGérard 2010 | 25% | 1% | P<0.001 |
| Local recurrenceIntention-to-treat analysis of all randomly assigned patients (598)3-year cumulative incidence of local recurrence | long term-updateGérard 2012 | 4.4% at 3 y | 6.1% at 3 y | The abstract states that there was no significant difference between CAP45 and CAPOX50 at 3 years; P values are not given. |
| OSIntention-to-treat analysis of all randomly assigned patients (598)3-year overall survival | long term-updateGérard 2012 | 88.3% at 3 y | 87.6% at 3 y | — |
| DFSIntention-to-treat analysis of all randomly assigned patients (598)3-year disease-free survival | long term-updateGérard 2012 | 72.7% at 3 y | 67.9% at 3 y | — |
| DFSRandomised patients (598); analysis population not stated in the abstractDisease-free survival at a median follow-up of 60.2 months (multivariate analysis) | long term-updatemedian follow-up 60.2 monthsAzria 2017 | — | — | HR 1.02 (95% CI 0.76–1.36)P=0.9Hazard ratio from a multivariate analysis; the abstract does not state which arm is the reference. |
| OSRandomised patients (598); analysis population not stated in the abstractOverall survival at a median follow-up of 60.2 months (multivariate analysis) | long term-updatemedian follow-up 60.2 monthsAzria 2017 | — | — | HR 0.87 (95% CI 0.66–1.15)P=0.3Hazard ratio from a multivariate analysis; the abstract does not state which arm is the reference. |
| Local recurrenceRandomised patients (598); analysis population not stated in the abstractLocal control at a median follow-up of 60.2 months (univariate analysis); the abstract does not define the event | long term-updatemedian follow-up 60.2 monthsAzria 2017 | — | — | HR 0.92 (95% CI 0.51–1.66)P=0.7Hazard ratio from a univariate analysis; the abstract does not state which arm is the reference. |
| Endpoint | Analysis | Capox 50 | Cap 45 | Effect |
|---|---|---|---|---|
| pCRRandomly assigned patients (598); analysis population not stated in the abstractComplete sterilization of the operative specimen (ypCR), the primary end point | primaryGérard 2010 | 19.2% | 13.9% | P=0.09When ypCR was combined with 'few residual cells', the rate was 28.9% with Cap 45 and 39.4% with Capox 50 (P=0.008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P=0.02). Surgery was performed in 98% of patients in both groups. |
| Grade 3-4 acute toxicityRandomly assigned patients (598); analysis population not stated in the abstractPreoperative grade 3 to 4 toxicity | primaryGérard 2010 | 25% | 1% | P<0.001 |
| Local recurrenceIntention-to-treat analysis of all randomly assigned patients (598)3-year cumulative incidence of local recurrence | long term-updateGérard 2012 | 4.4% at 3 y | 6.1% at 3 y | The abstract states that there was no significant difference between CAP45 and CAPOX50 at 3 years; P values are not given. |
| OSIntention-to-treat analysis of all randomly assigned patients (598)3-year overall survival | long term-updateGérard 2012 | 88.3% at 3 y | 87.6% at 3 y | — |
| DFSIntention-to-treat analysis of all randomly assigned patients (598)3-year disease-free survival | long term-updateGérard 2012 | 72.7% at 3 y | 67.9% at 3 y | — |
| DFSRandomised patients (598); analysis population not stated in the abstractDisease-free survival at a median follow-up of 60.2 months (multivariate analysis) | long term-updatemedian follow-up 60.2 monthsAzria 2017 | — | — | HR 1.02 (95% CI 0.76–1.36)P=0.9Hazard ratio from a multivariate analysis; the abstract does not state which arm is the reference. |
| OSRandomised patients (598); analysis population not stated in the abstractOverall survival at a median follow-up of 60.2 months (multivariate analysis) | long term-updatemedian follow-up 60.2 monthsAzria 2017 | — | — | HR 0.87 (95% CI 0.66–1.15)P=0.3Hazard ratio from a multivariate analysis; the abstract does not state which arm is the reference. |
| Local recurrenceRandomised patients (598); analysis population not stated in the abstractLocal control at a median follow-up of 60.2 months (univariate analysis); the abstract does not define the event | long term-updatemedian follow-up 60.2 monthsAzria 2017 | — | — | HR 0.92 (95% CI 0.51–1.66)P=0.7Hazard ratio from a univariate analysis; the abstract does not state which arm is the reference. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 1.02 | 0.76–1.36 |
| OS | 0.87 | 0.66–1.15 |
| Local recurrence | 0.92 | 0.51–1.66 |
Appears in
Sources
Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010;28(10):1638-44.
Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012;30(36):4558-65.
Azria D, Doyen J, Jarlier M, Martel-Lafay I, Hennequin C, Etienne P, et al. Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer. Ann Oncol. 2017;28(10):2436-2442.