IDEA
International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration: prospective pooled analysis of six randomised phase 3 trials of 3 versus 6 months of adjuvant FOLFOX or CAPOX in stage III colon cancer
Phase meta-analysisN = 12,834
- Population
- Patients with stage III colon cancer (pooled analysis of six randomised trials); 12,834 in the NEJM primary analysis and 12,835 in the final overall survival analysis; 5,064 received CAPOX and 7,771 FOLFOX in the final analysis.
- Design
- Prospective, preplanned pooled analysis of six randomised phase 3 trials run concurrently (CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, HORG), each comparing 3 with 6 months of adjuvant FOLFOX or CAPOX, the regimen chosen by the treating physician (and, in some trials, the patient) and not randomised. Primary endpoint 3-year disease-free survival; noninferiority of 3 months could be claimed if the upper limit of the two-sided 95% CI of the hazard ratio did not exceed 1.12. The prespecified overall survival margin was a hazard ratio of 1.11.
- Primary endpoint
- DFS
- Arms
- 6 months (control): 6 months of adjuvant FOLFOX or CAPOX
- 3 months (experimental): 3 months of adjuvant FOLFOX or CAPOX
- People
- Grothey A, IDEA Collaboration
DFSHR 1.07 (95% CI 1.00–1.15)DFSHR 0.95 (95% CI 0.85–1.06)DFSHR 1.16 (95% CI 1.06–1.26)Δ 36-month DFS−0.9 pointsDFSHR 1.01 (95% CI 0.90–1.12)Δ 36-month DFS−0.2 points
Show the numbers
| Endpoint | Analysis | 3 months | 6 months | Effect |
|---|---|---|---|---|
| DFSPatients with stage III colon cancer pooled from six trials (12,834); the NEJM abstract does not label the analysis population (the full text describes a modified intention-to-treat analysis of patients who received at least one dose) | primaryGrothey 2018 | — | — | HR 1.07 (95% CI 1.00–1.15)Noninferiority was not confirmed in the overall population. Hazard ratio above 1 favours 6 months. 3263 events of recurrence or death. |
| DFSPatients treated with CAPOX (regimen not randomised) | primaryGrothey 2018 | — | — | HR 0.95 (95% CI 0.85–1.06)Prespecified regimen subgroup. The 3-year DFS rates for CAPOX in the full text were 75.9 percent (3 months) and 74.8 percent (6 months). |
| DFSPatients treated with FOLFOX (regimen not randomised) | primaryGrothey 2018 | — | — | HR 1.16 (95% CI 1.06–1.26)Prespecified regimen subgroup. The 3-year DFS rates for FOLFOX (all stages combined) in the full text were 73.6 percent (3 months) and 76.0 percent (6 months). |
| DFSPatients with stage III colon cancer pooled from six trials (12,834); the NEJM abstract does not label the analysis population (the full text describes a modified intention-to-treat analysis of patients who received at least one dose) | primaryGrothey 2018 | 74.6% at 3 y (73.5–75.7%) | 75.5% at 3 y (74.4–76.7%) | Overall 3-year DFS rates are not in the abstract; read from the PMC author manuscript. |
| DFSExploratory subgroup: T1, T2 or T3 and N1 cancers, FOLFOX and CAPOX combined | exploratoryGrothey 2018 | 83.1% at 3 y | 83.3% at 3 y | HR 1.01 (95% CI 0.90–1.12)Exploratory; the full text states subgroup analyses were performed without adjustment for multiplicity. |
| DFSExploratory subgroup: T4, N2 or both, FOLFOX and CAPOX combined | exploratoryGrothey 2018 | 62.7% at 3 y | 64.4% at 3 y | HR 1.12 (95% CI 1.03–1.23)P=0.01 for superiorityExploratory; 6 months was superior to 3 months in this subgroup. Subgroup analyses were not adjusted for multiplicity. |
| DFSFinal analysis, modified intention-to-treat: patients with stage III colon cancer who started any treatment (12,835) | long term-updateAndré 2020 | — | — | HR 1.08 (95% CI 1.02–1.15)P=0.25Non-inferiority false-discovery-rate adjusted p value 0.25 (noninferiority not shown). |
| OSFinal analysis, modified intention-to-treat: patients with stage III colon cancer who started any treatment (12,835) | finalmedian follow-up 72.3 monthsAndré 2020 | 82.4% at 5 y (81.4–83.3%) | 82.8% at 5 y (81.8–83.8%) | HR 1.02 (95% CI 0.95–1.11)P=0.058Secondary endpoint; non-inferiority declared if the one-sided FDR-adjusted p value was below 0.025 (margin HR 1.11): 0.058, so noninferiority was not confirmed. 2584 deaths. The authors describe the absolute difference in 5-year OS as 0.4 percentage points. |
| OSPatients treated with CAPOX (modified intention-to-treat; regimen not randomised) | finalmedian follow-up 72.3 monthsAndré 2020 | 82.1% at 5 y (80.5–83.6%) | 81.2% at 5 y (79.2–82.9%) | HR 0.96 (95% CI 0.85–1.08)P=0.033Non-inferiority FDR-adjusted p value 0.033. |
| OSPatients treated with FOLFOX (modified intention-to-treat; regimen not randomised) | finalmedian follow-up 72.3 monthsAndré 2020 | 82.6% at 5 y (81.3–83.8%) | 83.8% at 5 y (82.6–85.0%) | HR 1.07 (95% CI 0.97–1.18)P=0.34Non-inferiority FDR-adjusted p value 0.34. |
| Endpoint | Analysis | 3 months | 6 months | Effect |
|---|---|---|---|---|
| DFSPatients with stage III colon cancer pooled from six trials (12,834); the NEJM abstract does not label the analysis population (the full text describes a modified intention-to-treat analysis of patients who received at least one dose) | primaryGrothey 2018 | — | — | HR 1.07 (95% CI 1.00–1.15)Noninferiority was not confirmed in the overall population. Hazard ratio above 1 favours 6 months. 3263 events of recurrence or death. |
| DFSPatients treated with CAPOX (regimen not randomised) | primaryGrothey 2018 | — | — | HR 0.95 (95% CI 0.85–1.06)Prespecified regimen subgroup. The 3-year DFS rates for CAPOX in the full text were 75.9 percent (3 months) and 74.8 percent (6 months). |
| DFSPatients treated with FOLFOX (regimen not randomised) | primaryGrothey 2018 | — | — | HR 1.16 (95% CI 1.06–1.26)Prespecified regimen subgroup. The 3-year DFS rates for FOLFOX (all stages combined) in the full text were 73.6 percent (3 months) and 76.0 percent (6 months). |
| DFSPatients with stage III colon cancer pooled from six trials (12,834); the NEJM abstract does not label the analysis population (the full text describes a modified intention-to-treat analysis of patients who received at least one dose) | primaryGrothey 2018 | 74.6% at 3 y (73.5–75.7%) | 75.5% at 3 y (74.4–76.7%) | Overall 3-year DFS rates are not in the abstract; read from the PMC author manuscript. |
| DFSExploratory subgroup: T1, T2 or T3 and N1 cancers, FOLFOX and CAPOX combined | exploratoryGrothey 2018 | 83.1% at 3 y | 83.3% at 3 y | HR 1.01 (95% CI 0.90–1.12)Exploratory; the full text states subgroup analyses were performed without adjustment for multiplicity. |
| DFSExploratory subgroup: T4, N2 or both, FOLFOX and CAPOX combined | exploratoryGrothey 2018 | 62.7% at 3 y | 64.4% at 3 y | HR 1.12 (95% CI 1.03–1.23)P=0.01 for superiorityExploratory; 6 months was superior to 3 months in this subgroup. Subgroup analyses were not adjusted for multiplicity. |
| DFSFinal analysis, modified intention-to-treat: patients with stage III colon cancer who started any treatment (12,835) | long term-updateAndré 2020 | — | — | HR 1.08 (95% CI 1.02–1.15)P=0.25Non-inferiority false-discovery-rate adjusted p value 0.25 (noninferiority not shown). |
| OSFinal analysis, modified intention-to-treat: patients with stage III colon cancer who started any treatment (12,835) | finalmedian follow-up 72.3 monthsAndré 2020 | 82.4% at 5 y (81.4–83.3%) | 82.8% at 5 y (81.8–83.8%) | HR 1.02 (95% CI 0.95–1.11)P=0.058Secondary endpoint; non-inferiority declared if the one-sided FDR-adjusted p value was below 0.025 (margin HR 1.11): 0.058, so noninferiority was not confirmed. 2584 deaths. The authors describe the absolute difference in 5-year OS as 0.4 percentage points. |
| OSPatients treated with CAPOX (modified intention-to-treat; regimen not randomised) | finalmedian follow-up 72.3 monthsAndré 2020 | 82.1% at 5 y (80.5–83.6%) | 81.2% at 5 y (79.2–82.9%) | HR 0.96 (95% CI 0.85–1.08)P=0.033Non-inferiority FDR-adjusted p value 0.033. |
| OSPatients treated with FOLFOX (modified intention-to-treat; regimen not randomised) | finalmedian follow-up 72.3 monthsAndré 2020 | 82.6% at 5 y (81.3–83.8%) | 83.8% at 5 y (82.6–85.0%) | HR 1.07 (95% CI 0.97–1.18)P=0.34Non-inferiority FDR-adjusted p value 0.34. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 1.07 | 1–1.15 |
| DFS | 0.95 | 0.85–1.06 |
| DFS | 1.16 | 1.06–1.26 |
| DFS | 1.01 | 0.9–1.12 |
| DFS | 1.12 | 1.03–1.23 |
| DFS | 1.08 | 1.02–1.15 |
| OS | 1.02 | 0.95–1.11 |
| OS | 0.96 | 0.85–1.08 |
| OS | 1.07 | 0.97–1.18 |
Appears in
Sources
Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med. 2018;378(13):1177-1188.
André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, et al. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020;21(12):1620-1629.