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

Author(s): Yukihide Kanemitsu, MD1; Yasuhiro Shimizu, MD, PhD2; Junki Mizusawa, PhD1; Yoshitaka Inaba, MD, PhD2; Shunsuke Tsukamoto, MD, PhD1; Atsuo Takashima, MD, PhD1; Masayuki Ohue, MD, PhD3; Koji Komori, MD, PhD2; Akio Shiomi, MD4; Manabu Shiozawa, MD, PhD5; Yusuke Suwa, MD, PhD6; Takeshi Suto, MD7; Yusuke Kinugasa, MD, PhD8; Yasumasa Takii, MD9; Hiroyuki Bando, MD, PhD10; Takaya Kobatake, MD11; Masafumi Inomata, MD, PhD12; Yasuhiro Shimada, MD13; Hiroshi Katayama, MD1; Haruhiko Fukuda, MD1; JCOG Colorectal Cancer Study Group;
Source: DOI: 10.1200/JCO-25-01231
Original Article
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Dr. Anjan Patel's Thoughts

The mature overall survival (OS) data from this Japanese randomized trial answer the question the initial publication left open, and the answer is no, adjuvant mFOLFOX6 after hepatectomy for resectable colorectal liver metastases does not improve overall survival (HR 1.07, P=.74), despite the previously reported DFS benefit. Five-year OS was numerically worse in the chemotherapy arm (73% vs 80%), though not significantly so. The disease-free survival (DFS) benefit was likely confounded by oxaliplatin-induced hepatic changes obscuring imaging and imbalances in post-recurrence therapy. Selection of patients and those with curable vs incurable intent surgery may have led to some bias in my opinion.

ABSTRACT

AbstractJCOG0603 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. 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.

Author Affiliations

1National Cancer Center Hospital, Tokyo, Japan; 2Aichi Cancer Center Hospital, Nagoya, Japan; 3Osaka International Cancer Institute, Osaka, Japan; 4Shizuoka Cancer Center Hospital, Shizuoka, Japan; 5Kanagawa Cancer Center, Kanagawa, Japan; 6Yokohama City University Medical Center, Yokohama, Japan; 7Yamagata Prefectural Central Hospital, Yamagata, Japan; 8Institute of Science Tokyo, Tokyo, Japan; 9Niigata Cancer Center Hospital, Niigata, Japan; 10Ishikawa Prefectural Central Hospital, Kanazawa, Japan; 11National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan; 12Oita University Faculty of Medicine, Yufu, Japan; 13Kochi Health Sciences Center, Kochi, Japan

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