MOSAIC
Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer
Phase 3N = 2,246NCT00275210
- Population
- Patients who had undergone curative resection for stage II or III colon cancer; 2246 randomly assigned, 1123 to each group. Mismatch repair status and BRAF mutation were assessed in 1,008 tumour specimens for the 2015 update.
- Design
- Randomised comparison of six months of bolus plus continuous-infusion fluorouracil with leucovorin (LV5FU2) with or without oxaliplatin (FOLFOX4) after curative resection of stage II or III colon cancer. Primary endpoint disease-free survival; secondary endpoints overall survival and safety. The 2009 and 2015 reports are updates of the same randomised cohort.
- Primary endpoint
- DFS
- Arms
- LV5FU2 (control, n = 1,123): Bolus plus continuous-infusion fluorouracil with leucovorin (LV5FU2) for 6 months
- FOLFOX4 (experimental, n = 1,123): LV5FU2 plus oxaliplatin (FOLFOX4) for 6 months
- People
- André T, MOSAIC Investigators
DFSHR 0.77Δ 36-month DFS+5.3 pointsDFSHR 0.80 (95% CI 0.68–0.93)Δ 60-month DFS+5.9 pointsOSHR 0.84 (95% CI 0.71–1.00)Δ 72-month OS+2.5 points
Show the numbers
| Endpoint | Analysis | FOLFOX4 | LV5FU2 | Effect |
|---|---|---|---|---|
| DFSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | primarymedian follow-up 37.9 monthsAndré 2004 | 78.2% at 3 y (75.6–80.7%) | 72.9% at 3 y (70.2–75.7%) | HR 0.77P=0.002The abstract gives the hazard ratio 'for recurrence' without a confidence interval. Cancer-related events: 237 (21.1 percent) with oxaliplatin and 293 (26.1 percent) without. |
| DFSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | long term-updateAndré 2009 | 73.3% at 5 y | 67.4% at 5 y | HR 0.80 (95% CI 0.68–0.93)P=0.003 |
| OSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | long term-updateAndré 2009 | 78.5% at 6 y | 76% at 6 y | HR 0.84 (95% CI 0.71–1.00)P=0.046Secondary endpoint. The upper bound of the confidence interval is 1.00. |
| OSStage III subgroup of the randomised cohort | long term-updateAndré 2009 | 72.9% at 6 y | 68.7% at 6 y | HR 0.80 (95% CI 0.65–0.97)P=0.023Subgroup. The abstract states that no OS difference was seen in the stage II population and gives no figures for it. |
| OSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | long term-updatemedian follow-up 9.5 yearsAndré 2015 | 71.7% at 10 y | 67.1% at 10 y | HR 0.85P=0.043The abstract gives no confidence interval for this hazard ratio. |
| OSStage II subgroup of the randomised cohort | long term-updatemedian follow-up 9.5 yearsAndré 2015 | 78.4% at 10 y | 79.5% at 10 y | HR 1P=0.980Subgroup. The abstract gives no confidence interval for this hazard ratio. |
| OSStage III subgroup of the randomised cohort | long term-updatemedian follow-up 9.5 yearsAndré 2015 | 67.1% at 10 y | 59% at 10 y | HR 0.8P=0.016Subgroup. The abstract gives no confidence interval for this hazard ratio. |
| DFSPatients with dMMR tumours (95 of 1,008 tested specimens), stages II to III | exploratoryAndré 2015 | — | — | HR 0.48 (95% CI 0.20–1.12)Exploratory biomarker analysis; the confidence interval includes 1. Ninety-five patients (9.4 percent; 95 of the 1,008 tested specimens) had dMMR tumours. |
| OSPatients with dMMR tumours (95 of 1,008 tested specimens), stages II to III | exploratoryAndré 2015 | — | — | HR 0.41 (95% CI 0.16–1.07)Exploratory biomarker analysis; the confidence interval includes 1. |
| Grade 3 sensory neuropathyPatients treated with FL plus oxaliplatin; denominator not stated in the abstract | primaryAndré 2004 | 12.4% | — | 12.4 percent during treatment; the abstract reports 1.1 percent at one year of follow-up in the same group. |
| Grade 3 sensory neuropathyPatients who received oxaliplatin; denominator not stated in the abstract | long term-updateAndré 2009 | 1.3% | — | 1.3 percent at 12 months after treatment; 0.7 percent at 48 months. |
| Endpoint | Analysis | FOLFOX4 | LV5FU2 | Effect |
|---|---|---|---|---|
| DFSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | primarymedian follow-up 37.9 monthsAndré 2004 | 78.2% at 3 y (75.6–80.7%) | 72.9% at 3 y (70.2–75.7%) | HR 0.77P=0.002The abstract gives the hazard ratio 'for recurrence' without a confidence interval. Cancer-related events: 237 (21.1 percent) with oxaliplatin and 293 (26.1 percent) without. |
| DFSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | long term-updateAndré 2009 | 73.3% at 5 y | 67.4% at 5 y | HR 0.80 (95% CI 0.68–0.93)P=0.003 |
| OSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | long term-updateAndré 2009 | 78.5% at 6 y | 76% at 6 y | HR 0.84 (95% CI 0.71–1.00)P=0.046Secondary endpoint. The upper bound of the confidence interval is 1.00. |
| OSStage III subgroup of the randomised cohort | long term-updateAndré 2009 | 72.9% at 6 y | 68.7% at 6 y | HR 0.80 (95% CI 0.65–0.97)P=0.023Subgroup. The abstract states that no OS difference was seen in the stage II population and gives no figures for it. |
| OSRandomised patients with stage II or III colon cancer after curative resection (2246); the analysis population is not labelled in the abstract | long term-updatemedian follow-up 9.5 yearsAndré 2015 | 71.7% at 10 y | 67.1% at 10 y | HR 0.85P=0.043The abstract gives no confidence interval for this hazard ratio. |
| OSStage II subgroup of the randomised cohort | long term-updatemedian follow-up 9.5 yearsAndré 2015 | 78.4% at 10 y | 79.5% at 10 y | HR 1P=0.980Subgroup. The abstract gives no confidence interval for this hazard ratio. |
| OSStage III subgroup of the randomised cohort | long term-updatemedian follow-up 9.5 yearsAndré 2015 | 67.1% at 10 y | 59% at 10 y | HR 0.8P=0.016Subgroup. The abstract gives no confidence interval for this hazard ratio. |
| DFSPatients with dMMR tumours (95 of 1,008 tested specimens), stages II to III | exploratoryAndré 2015 | — | — | HR 0.48 (95% CI 0.20–1.12)Exploratory biomarker analysis; the confidence interval includes 1. Ninety-five patients (9.4 percent; 95 of the 1,008 tested specimens) had dMMR tumours. |
| OSPatients with dMMR tumours (95 of 1,008 tested specimens), stages II to III | exploratoryAndré 2015 | — | — | HR 0.41 (95% CI 0.16–1.07)Exploratory biomarker analysis; the confidence interval includes 1. |
| Grade 3 sensory neuropathyPatients treated with FL plus oxaliplatin; denominator not stated in the abstract | primaryAndré 2004 | 12.4% | — | 12.4 percent during treatment; the abstract reports 1.1 percent at one year of follow-up in the same group. |
| Grade 3 sensory neuropathyPatients who received oxaliplatin; denominator not stated in the abstract | long term-updateAndré 2009 | 1.3% | — | 1.3 percent at 12 months after treatment; 0.7 percent at 48 months. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.8 | 0.68–0.93 |
| OS | 0.84 | 0.71–1 |
| OS | 0.8 | 0.65–0.97 |
| DFS | 0.48 | 0.2–1.12 |
| OS | 0.41 | 0.16–1.07 |
Appears in
Sources
André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343-51.
André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27(19):3109-16.
André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. J Clin Oncol. 2015;33(35):4176-87.