Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported for OS comparison

• Effect Size: 5-year DFS: 49.7% vs 40.5%; 5-year OS: 73.4% vs 80.1%

• Primary Outcome: Disease-free survival: HR 0.72 (95% CI 0.54-0.97) favoring adjuvant chemotherapy

• Nnt Or Sensitivity: Approximately 11 patients need treatment to prevent one recurrence at 5 years

• Confidence Interval: OS HR 1.07 (95% CI 0.73-1.57)

Clinical Application

Standard hepatectomy and mFOLFOX6 regimen readily available in Australian tertiary centers Relevant to Australian practice; mFOLFOX6 available on PBS for colorectal cancer; aligns with multidisciplinary team approach recommended by Cancer Australia guidelines Patients with resectable colorectal liver metastases suitable for hepatectomy and adjuvant chemotherapy

Abstract

JCOG0603 demonstrated improved disease-free survival (DFS) with adjuvant mFOLFOX6 after hepatectomy compared with hepatectomy alone in colorectal liver-only metastasis (CRLM), but the overall survival (OS) data were immature. Here, we report OS after long-term follow-up. Eligible patients with colorectal adenocarcinoma and an unlimited number of liver metastases were randomized to adjuvant mFOLFOX6 or hepatectomy alone. DFS was the primary endpoint, and OS was a secondary endpoint. Between March 2007 and January 2019, 151 and 149 patients were randomized to adjuvant chemotherapy and hepatectomy alone, respectively. At a median follow-up of 7.7 years for disease-free surviving patients, 54 (35.8%) and 51 (34.2%) patients had died in the respective arms, (hazard ratio [HR], 1.07 [95% CI, 0.73 to 1.57]). Five-year OS was 73.4% (95% CI, 65.5 to 79.7) and 80.1% (95% CI, 72.6 to 85.7) and 7-year OS was 69.4% (95% CI, 61.2 to 76.2) and 72.4% (95% CI, 64.2 to 79.1), respectively. One patient in the adjuvant chemotherapy arm possibly died of protocol treatment-related toxicity, and one in the hepatectomy-alone arm died of post-protocol treatment complications. Five-year DFS was respectively 49.7% (95% CI, 41.5 to 57.3) and 40.5% (95% CI, 32.5 to 48.3) in the adjuvant chemotherapy and hepatectomy-alone arms (HR, 0.72 [95% CI, 0.54 to 0.97]). Long-term OS did not differ with adjuvant mFOLFOX6 compared with hepatectomy alone in resectable CRLM. Adjuvant mFOLFOX6 may delay recurrence but did not improve long-term survival.

References

1. 1.Kanemitsu, Y., Shimizu, Y., Mizusawa, J., Inaba, Y., Tsukamoto, S., Takashima, A., Ohue, M., Komori, K., Shiomi, A., Shiozawa, M., Suwa, Y., Suto, T., Kinugasa, Y., Takii, Y., Bando, H., Kobatake, T., Inomata, M., Shimada, Y., Katayama, H., & Fukuda, H. (2026). Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01231