In the Japanese phase II/III JCOG0603 trial reported in the Journal of Clinical Oncology, Kanemitsu et al found that the addition of adjuvant mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) to hepatectomy improved disease-free survival in patients with liver-only metastatic colorectal cancer; however, overall survival was numerically poorer in the adjuvant chemotherapy group.
In the open-label multicenter trial, 300 patients with any number of liver metastases were randomly assigned between March 2007 and January 2019 to hepatectomy followed by 12 cycles of mFOLFOX6 (n = 151) or hepatectomy alone (n = 149). The primary endpoint was disease-free survival.
Disease-Free and Overall Survival
At the third interim analysis, with a median follow-up of 53.6 months, the trial was terminated early according to protocol on the basis of significantly prolonged disease-free survival in the hepatectomy/chemotherapy group vs the hepatectomy group.
Disease-free survival was 52.1% (95% confidence interval [CI] = 43.2%–60.2%) vs 41.5% (95% CI = 33.2%–49.6%) at 3 years and 50.1% (95% CI = 41.2%–58.4%) vs 37.3% (95% CI = 28.9%–45.6%) at 5 years (hazard ratio [HR] = 0.63, 95% CI = 0.49–0.92, P = .002).
At an updated analysis with a median follow-up of 59.2 months, 5-year disease-free survival was 49.8% (95% CI = 41.0%–58.0%) vs 38.7% (95% CI = 30.4%–46.8%; HR = 0.67, 95% CI = 0.50–0.92, P =.006).
At the updated analysis, overall survival was 87.2% (95% CI = 80.2%–91.9%) vs 91.8% (95% CI = 85.7%–95.4%) at 3 years and 71.2% (95% CI = 61.7%–78.8%) vs 83.1% (95% CI = 74.9%–88.9%) at 5 years (HR = 1.25, 95% CI = 0.78–2.00, P = .42).
The most common grade ≥ 3 adverse events in the chemotherapy group were neutropenia (50%), sensory neuropathy (10%), and allergic reactions (4%). The incidence of any-grade postoperative complications was similar in the two groups. One patient died from unknown cause after three cycles of mFOLFOX6.
The investigators concluded, “Disease-free survival did not correlate with overall survival for liver-only metastatic colorectal cancer. Adjuvant chemotherapy with mFOLFOX6 improves disease-free survival among patients treated with hepatectomy for colorectal cancer liver metastasis. It remains unclear whether chemotherapy improves overall survival.”
Yukihide Kanemitsu, MD, of the Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Research and Development Funds, a Health and Labor Sciences Research Grant for Clinical Cancer Research, and Japan Agency for Medical Research and Development. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.