Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Surgery and Science, Kyushu University, Fukuoka, Japan.
J Clin Oncol. 2022 Oct 10;40(29):3419-3429. doi: 10.1200/JCO.21.02628. Epub 2022 May 5.
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.
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.
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; = .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% 8%, respectively), and in those receiving mFOLFOX6 compared with CAPOX (14% 11%, respectively).
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.
在日本进行的 III 期 ACHIEVE 试验是国际辅助治疗持续时间评估合作组织纳入的六项前瞻性研究之一，旨在探讨辅助氟尿嘧啶、亚叶酸钙和奥沙利铂（FOLFOX）或卡培他滨和奥沙利铂（CAPOX）治疗 3 个月与 6 个月在可切除 III 期结肠癌患者中的疗效是否相当。我们报告了生存和长期安全性的最终分析结果。
符合条件的患者以 1:1 的比例随机分配（修改后）接受 3 或 6 个月的辅助化疗（根据治疗医生选择的改良 [m]FOLFOX6 或 CAPOX）。随机分组根据受累淋巴结数量、中心、方案、原发部位和年龄进行分层。主要终点是无病生存，在修改后的意向治疗人群中进行评估。总生存（OS）是次要终点。
修改后的意向治疗人群包括 1291 名患者：6 个月治疗组 641 名，3 个月治疗组 650 名。本次分析的中位随访时间为 74.7 个月。5 年 OS 率相当：3 个月治疗组为 87.0%，6 个月治疗组为 86.4%（风险比，0.91；95%CI，0.69 至 1.20；P=0.51）。OS 的亚组分析未显示基线特征和治疗持续时间之间存在显著的相互作用。与 3 个月治疗组相比，6 个月治疗组（分别为 16%和 8%）和接受 mFOLFOX6 治疗的患者（分别为 14%和 11%）中，持续时间超过 5 年的周围感觉神经病变更为常见。
在亚洲患者中，将辅助治疗时间从 6 个月缩短至 3 个月不会影响疗效，并降低长期周围感觉神经病变的发生率。在这种情况下，3 个月的 CAPOX 治疗是一种合适的辅助治疗选择。
