JCOG0603
Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial
Phase 2/3N = 300
- Population
- Liver-only metastatic colorectal cancer treated by hepatectomy
- Design
- Randomised phase II or III trial (UMIN000000653; also jRCTs031180285 per the 2026 full text; 46 hospitals in Japan): patients aged 20 to 75 years with confirmed colorectal cancer and an unlimited number of liver-only metastases were randomly assigned to hepatectomy alone or to hepatectomy followed by 12 courses of adjuvant mFOLFOX6. The primary endpoint of phase III was disease-free survival (intention to treat); overall survival was secondary. 300 patients were randomised between March 2007 and January 2019 (149 hepatectomy alone, 151 hepatectomy plus chemotherapy). The trial was stopped early at the third interim analysis of phase III (median follow-up 53.6 months).
- Primary endpoint
- DFS
- Arms
- Hepatectomy alone (control, n = 149): Hepatectomy alone
- Hepatectomy plus mFOLFOX6 (experimental, n = 151): Hepatectomy followed by 12 courses of adjuvant mFOLFOX6
- People
- Kanemitsu Y
DFSHR 0.67 (95% CI 0.50–0.92)Δ 60-month DFS+11.1 pointsΔ 60-month OS−11.9 pointsDFSHR 0.72 (95% CI 0.54–0.97)Δ 60-month DFS+9.2 pointsOSHR 1.07 (95% CI 0.73–1.57)
Show the numbers
| Endpoint | Analysis | Hepatectomy plus mFOLFOX6 | Hepatectomy alone | Effect |
|---|---|---|---|---|
| DFS | interimmedian follow-up 59.2 monthsKanemitsu 2021 | 49.8% at 5 y (41–58%) | 38.7% at 5 y (30.4–46.8%) | HR 0.67 (95% CI 0.50–0.92)P=0.006 (one-sided)Updated 5-year disease-free survival at a median follow-up of 59.2 months, reported after the trial was stopped early at the third interim analysis (median follow-up 53.6 months) because disease-free survival was significantly longer with chemotherapy. |
| OSAll randomised patients (analysis population not stated in the abstract) | interimmedian follow-up 59.2 monthsKanemitsu 2021 | 71.2% at 5 y (61.7–78.8%) | 83.1% at 5 y (74.9–88.9%) | Updated 5-year overall survival at a median follow-up of 59.2 months; the abstract gives no hazard ratio and states that it remains unclear whether chemotherapy improves overall survival. Overall survival was a secondary endpoint; the 2026 long-term report describes these overall survival data as immature. |
| DFSAll randomised patients (intention-to-treat per the 2026 full text) | long term-updatemedian follow-up 7.7 yearsKanemitsu 2026 | 49.7% at 5 y (41.5–57.3%) | 40.5% at 5 y (32.5–48.3%) | HR 0.72 (95% CI 0.54–0.97)Long-term follow-up (JCO 2026); median follow-up of 7.7 years is for disease-free surviving patients; five-year disease-free survival in the adjuvant chemotherapy and hepatectomy-alone arms. |
| OSAll randomised patients (intention-to-treat per the 2026 full text) | long term-updatemedian follow-up 7.7 yearsKanemitsu 2026 | 73.4% at 5 y (65.5–79.7%); 69.4% at 7 y (61.2–76.2%) | 80.1% at 5 y (72.6–85.7%); 72.4% at 7 y (64.2–79.1%) | HR 1.07 (95% CI 0.73–1.57)Overall survival after long-term follow-up (JCO 2026); median follow-up of 7.7 years is for disease-free surviving patients. Deaths: 54 (35.8%) with adjuvant chemotherapy and 51 (34.2%) with hepatectomy alone. Overall survival was a secondary endpoint. The hazard ratio is for adjuvant chemotherapy relative to hepatectomy alone: the paper does not word the direction, but it follows from the death counts and the 5- and 7-year survival estimates and from the disease-free survival ratio, which is stated for chemotherapy against hepatectomy alone. The five-year estimates differ from those in the 2021 report (83.1% and 71.2%). |
| Endpoint | Analysis | Hepatectomy plus mFOLFOX6 | Hepatectomy alone | Effect |
|---|---|---|---|---|
| DFS | interimmedian follow-up 59.2 monthsKanemitsu 2021 | 49.8% at 5 y (41–58%) | 38.7% at 5 y (30.4–46.8%) | HR 0.67 (95% CI 0.50–0.92)P=0.006 (one-sided)Updated 5-year disease-free survival at a median follow-up of 59.2 months, reported after the trial was stopped early at the third interim analysis (median follow-up 53.6 months) because disease-free survival was significantly longer with chemotherapy. |
| OSAll randomised patients (analysis population not stated in the abstract) | interimmedian follow-up 59.2 monthsKanemitsu 2021 | 71.2% at 5 y (61.7–78.8%) | 83.1% at 5 y (74.9–88.9%) | Updated 5-year overall survival at a median follow-up of 59.2 months; the abstract gives no hazard ratio and states that it remains unclear whether chemotherapy improves overall survival. Overall survival was a secondary endpoint; the 2026 long-term report describes these overall survival data as immature. |
| DFSAll randomised patients (intention-to-treat per the 2026 full text) | long term-updatemedian follow-up 7.7 yearsKanemitsu 2026 | 49.7% at 5 y (41.5–57.3%) | 40.5% at 5 y (32.5–48.3%) | HR 0.72 (95% CI 0.54–0.97)Long-term follow-up (JCO 2026); median follow-up of 7.7 years is for disease-free surviving patients; five-year disease-free survival in the adjuvant chemotherapy and hepatectomy-alone arms. |
| OSAll randomised patients (intention-to-treat per the 2026 full text) | long term-updatemedian follow-up 7.7 yearsKanemitsu 2026 | 73.4% at 5 y (65.5–79.7%); 69.4% at 7 y (61.2–76.2%) | 80.1% at 5 y (72.6–85.7%); 72.4% at 7 y (64.2–79.1%) | HR 1.07 (95% CI 0.73–1.57)Overall survival after long-term follow-up (JCO 2026); median follow-up of 7.7 years is for disease-free surviving patients. Deaths: 54 (35.8%) with adjuvant chemotherapy and 51 (34.2%) with hepatectomy alone. Overall survival was a secondary endpoint. The hazard ratio is for adjuvant chemotherapy relative to hepatectomy alone: the paper does not word the direction, but it follows from the death counts and the 5- and 7-year survival estimates and from the disease-free survival ratio, which is stated for chemotherapy against hepatectomy alone. The five-year estimates differ from those in the 2021 report (83.1% and 71.2%). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.67 | 0.5–0.92 |
| DFS | 0.72 | 0.54–0.97 |
| OS | 1.07 | 0.73–1.57 |
- Hepatectomy alone (control)
- Hepatectomy plus mFOLFOX6 (experimental)
Data table (modelled values)
| Months | Hepatectomy alone | Hepatectomy plus mFOLFOX6 |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 23 | 92.3% | 89.1% |
| 45 | 85.0% | 78.9% |
| 68 | 77.5% | 71.6% |
| 91 | 72.4% | 69.4% |
Appears in
Sources
Kanemitsu Y, Shimizu Y, Mizusawa J, Inaba Y, Hamaguchi T, Shida D, et al. Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial. J Clin Oncol. 2021;39(34):3789-3799.
Kanemitsu Y, Shimizu Y, Mizusawa J, Inaba Y, Tsukamoto S, Takashima A, et al. Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603. J Clin Oncol. 2026;44(15):1395-1400.