Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest
Phase 3N = 244NCT01219920
- Population
- Previously untreated unresectable metastatic colorectal cancer, age 18 to 75 years
- Design
- Randomised phase 3 trial of FOLFOXIRI (irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 as a 48-hour continuous infusion starting on day 1, every 2 weeks) versus FOLFIRI as first-line treatment of unresectable metastatic colorectal cancer in patients aged 18 to 75 years with no prior chemotherapy for advanced disease. The primary endpoint was response rate. 244 patients were randomly assigned.
- Primary endpoint
- ORR
- Arms
- FOLFIRI (control): FOLFIRI (infusional fluorouracil, leucovorin, irinotecan)
- FOLFOXIRI (experimental): FOLFOXIRI (infusional fluorouracil, leucovorin, oxaliplatin, irinotecan)
- People
- Falcone A
Δ ORR+25 pointsPFSHR 0.63Δ median PFS+2.9 monthsOSHR 0.7Δ median OS+5.9 months
Show the numbers
| Endpoint | Analysis | FOLFOXIRI | FOLFIRI | Effect |
|---|---|---|---|---|
| ORRAll randomised patients (analysis population not stated in the abstract) | primaryFalcone 2007 | 66% | 41% | P=0.0002Primary endpoint (response rate), investigator-assessed: complete 6% and 8%, partial 35% and 58% (FOLFIRI and FOLFOXIRI). Response confirmed by an external panel: 34% versus 60% (P<0.0001). |
| PFSAll randomised patients (analysis population not stated in the abstract) | primaryFalcone 2007 | median 9.8 months | median 6.9 months | HR 0.63P=0.0006Not the primary endpoint; no confidence interval is given in the abstract. |
| OSAll randomised patients (analysis population not stated in the abstract) | primaryFalcone 2007 | median 22.6 months | median 16.7 months | HR 0.7P=0.032Not the primary endpoint; no confidence interval is given in the abstract. |
| Endpoint | Analysis | FOLFOXIRI | FOLFIRI | Effect |
|---|---|---|---|---|
| ORRAll randomised patients (analysis population not stated in the abstract) | primaryFalcone 2007 | 66% | 41% | P=0.0002Primary endpoint (response rate), investigator-assessed: complete 6% and 8%, partial 35% and 58% (FOLFIRI and FOLFOXIRI). Response confirmed by an external panel: 34% versus 60% (P<0.0001). |
| PFSAll randomised patients (analysis population not stated in the abstract) | primaryFalcone 2007 | median 9.8 months | median 6.9 months | HR 0.63P=0.0006Not the primary endpoint; no confidence interval is given in the abstract. |
| OSAll randomised patients (analysis population not stated in the abstract) | primaryFalcone 2007 | median 22.6 months | median 16.7 months | HR 0.7P=0.032Not the primary endpoint; no confidence interval is given in the abstract. |
- FOLFIRI (control)
- FOLFOXIRI (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | FOLFIRI | FOLFOXIRI |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 54.7% | 65.4% |
| 12 | 30.0% | 42.8% |
| 18 | 16.4% | 28.0% |
| 25 | 8.1% | 17.1% |
- FOLFIRI (control)
- FOLFOXIRI (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | FOLFIRI | FOLFOXIRI |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 55.9% | 65.1% |
| 28 | 31.3% | 42.4% |
| 42 | 17.5% | 27.6% |
| 57 | 9.4% | 17.4% |
Appears in
Sources
Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670-6.