Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial

Author(s): Takayuki Yoshino , MD, PhD¹; Eiji Oki , MD, PhD²; Toshihiro Misumi, PhD³; Masahito Kotaka , MD, PhD⁴; Dai Manaka , MD, PhD⁵; Tetsuya Eto, MD⁶; Junichi Hasegawa, MD, PhD⁷; Akinori Takagane , MD, PhD⁸; Masato Nakamura, MD, PhD⁹; Takeshi Kato, MD, PhD¹⁰; Yoshinori Munemoto , MD, PhD¹¹; Fumitaka Nakamura, MD, PhD¹²; Hiroyuki Bando , MD, PhD¹³; Hiroki Taniguchi, MD, PhD¹⁴; Yasuhiro Sakamoto, MD, PhD¹⁵; Manabu Shiozawa, MD, PhD¹⁶; Masayasu Nishi, MD, PhD¹⁷; Tetsuya Horiuchi, MD, PhD¹⁸; Hisakazu Yamagishi, MD, PhD¹⁹; Junichi Sakamoto, MD, PhD¹⁹; Tsunekazu Mizushima , MD, PhD²⁰; Atsushi Ohtsu, MD, PhD²¹; and Masaki Mori, MD, PhD²²

Source: DOI: 10.1200/JCO.21.02628 Journal of Clinical Oncology

Another study to support use of 3 months of CAPOX in lower-risk stage III colon cancer patients. Less toxicity and cost are likely observed in practice.

The phase III ACHIEVE trial conducted in Japan was one of six prospective studies included in the International Duration Evaluation of Adjuvant Therapy collaboration, which explored whether 3 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) therapy would be noninferior to 6 months of treatment in patients with curatively resected stage III colon cancer. We report the final analyses of survival and long-term safety.

PATIENTS AND METHODS

Eligible patients were randomly assigned (1:1) to either 3 or 6 months of adjuvant chemotherapy (modified [m]FOLFOX6 or CAPOX, as selected by the treating physician). Random assignment was stratified according to number of involved lymph nodes, center, regimen, primary site, and age. The primary end point was disease-free survival, assessed in the modified intention-to-treat population. Overall survival (OS) was a secondary end point.

RESULTS

The modified intention-to-treat population comprised 1,291 patients: 641 in the 6-month treatment group and 650 in the 3-month treatment group. Median follow-up for this analysis was 74.7 months. Five-year OS rates were comparable: 87.0% in the 3-month treatment group and 86.4% in the 6-month treatment group (hazard ratio, 0.91; 95% CI, 0.69 to 1.20; P = .51). Subgroup analysis of OS did not reveal a significant interaction between baseline characteristics and treatment duration. Peripheral sensory neuropathy lasting longer than 5 years was more common in the 6- compared with 3-month treatment group (16% v 8%, respectively), and in those receiving mFOLFOX6 compared with CAPOX (14% v 11%, respectively).

CONCLUSION

In Asian patients, shortening adjuvant therapy duration from 6 to 3 months did not compromise efficacy and reduced the rate of long-lasting peripheral sensory neuropathy. In this setting, 3 months of CAPOX therapy is an appropriate adjuvant treatment option.

Author Affiliations

¹Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan ²Department of Surgery and Science, Kyushu University, Fukuoka, Japan ³Department of Data Science, National Cancer Center Hospital East, Kashiwa, Japan ⁴Department of Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan ⁵Department of Surgery, Gastrointestinal Center, Kyoto Katsura Hospital, Kyoto, Japan ⁶Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan ⁷Department of Surgery, Osaka Rosai Hospital, Osaka, Japan ⁸Department of Surgery, Hakodate Goryoukaku Hospital, Hakodate, Japan ⁹Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan 10Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan 11Department of Surgery, Fukui-ken Saiseikai Hospital, Fukui, Japan 12Department of Surgery, Teine Keijinkai Hospital, Sapporo, Japan 13Gastroenterological Surgery, Ishikawa Prefectural Central Hospital,Kanazawa, Japan 14Department of Surgery, Kyoto Second Red Cross Hospital, Kyoto, Japan 15Department of Medical Oncology, Osaki Citizen Hospital, Osaki, Japan 16Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan 17Department of Gastroenterological Surgery, Hyogo Cancer Center, Akashi, Japan 18Department of Surgery, National Hospital Organization, Osaka Minami Medical Center, Kawachinagano, Japan 19Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan 20Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan 21National Cancer Center Hospital East, Kashiwa, Japan 22Tokai University School of Medicine, Isehara, Japan

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