536P - A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone for liver metastasis from colorectal cancer: Long-term results of JCOG0603

Background

JCOG0603 failed to demonstrate the improvement of adjuvant modified FOLFOX (mFOLFOX) after hepatectomy to hepatectomy alone in overall survival (OS) for liver only metastases from colorectal cancer (LM), even though mFOLFOX6 improved disease-free survival (DFS) over surgery alone. We report OS data after long-term follow-up with a cut-off date of Jan 2024.

Methods

This randomized phase II/III study enrolled patients (pts) from 46 hospitals in Japan. Eligible pts aged 20-75 years who had histologically proven colorectal adenocarcinoma with unlimited number of LM were randomized (1:1) to either adjuvant mFOLFOX6 (oxaliplatin 85 mg/m² with l-LV 200 mg/m² over 2 h followed by 5-FU 400 mg/m² bolus and 2400 mg/m² continuous infusion over 48 h) for 12 cycles after surgery arm or surgery alone arm. The primary endpoint of phase III was DFS. The secondary endpoints were OS and incidence of adverse events.

Results

Between Mar. 2007 and Jan. 2019, 300 pts were randomized. 151 pts were allocated to the adjuvant chemotherapy arm, and 149 pts to the surgery alone arm. At a median follow-up of 7.7 years (IQR 6.0–10.9) for surviving pts without disease, 54 (35.8%) pts in the chemotherapy arm had died versus 51 (34.2%) in the surgery alone arm (HR 1.07, 95% CI 0.73–1.57). Five-year OS was 73.4% (95% CI 65.5–79.7) in the chemotherapy arm versus 80.1% (72.6–85.7) in the surgery alone arm. Seven-year OS was 69.4% (61.2–76.2) in the chemotherapy arm versus 72.4% (64.2–79.1) in the surgery alone arm. One patient in the chemotherapy arm died possibly as a result of toxicity of protocol treatment, and one patient in the surgery alone arm died from complications due to post-trial therapy. The updated 5-year DFS was 49.7% (41.5-57.3) in the chemotherapy arm and 40.5% (32.5 – 48.3) in the surgery alone arm (HR 0.72 [0.54-0.97]).

Conclusions

Long-term observation of the JCOG0603 showed no difference in overall survival with the addition of adjuvant chemotherapy with mFOLFOX6 compared with surgery alone for pts with resectable liver metastases from colorectal cancer. Although adjuvant chemotherapy after hepatectomy may delay recurrence, the treatment did not improve long-term survival.

Clinical trial identification

UMIN000000653; jRCTs031180285.

Editorial acknowledgement

Legal entity responsible for the study

The Japan Clinical Oncology Group (JCOG).

Funding

Supported by National Cancer Research and Development Funds (23-A-19, 26-A-4, 29-A-3, 2020-J-3), a Health and Labour Sciences Research Grant for Clinical Cancer Research (H19-024), and AMED under Grant Numbers JP16ck0106047 and JP19ck0106308.

Disclosure

All authors have declared no conflicts of interest.