奥沙利铂联合氟尿嘧啶/贝伐珠单抗作为不可切除转移性结直肠癌老年患者初始治疗：一项多中心、随机、开放标签 III 期试验（JCOG1018）。

Oxaliplatin Added to Fluoropyrimidine/Bevacizumab as Initial Therapy for Unresectable Metastatic Colorectal Cancer in Older Patients: A Multicenter, Randomized, Open-Label Phase III Trial (JCOG1018).

机构信息

Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.

Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan.

出版信息

J Clin Oncol. 2024 Nov 20;42(33):3967-3976. doi: 10.1200/JCO.23.02722. Epub 2024 Aug 26.

DOI:10.1200/JCO.23.02722

PMID:39186709

Abstract

PURPOSE

Doublet chemotherapy with fluoropyrimidine (FP) and oxaliplatin (OX) plus bevacizumab (BEV) is a standard regimen for unresectable metastatic colorectal cancer (MCRC). However, the efficacy of adding OX to FP plus BEV (FP + BEV) remains unclear for older patients, a population for whom FP + BEV is standard. We aimed to confirm the superiority of adding OX to FP + BEV for this population.

METHODS

This open-label, randomized, phase III trial was conducted at 42 institutions in Japan. Patients with unresectable MCRC age 70-74 years with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 and those 75 years and older with ECOG-PS 0-2 were randomly assigned (1:1) to an FP + BEV arm or an OX addition (FP + BEV + OX) arm. Fluorouracil plus levofolinate calcium or capecitabine was declared before enrollment. The primary end point was progression-free survival (PFS). The study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031180145).

RESULTS

Between September 2012 and March 2019, 251 patients were randomly assigned to the FP + BEV arm (n = 125) and the FP + BEV + OX arm (n = 126). The median age was 80 and 79 years in the respective arm. The median PFS was 9.4 months (95% CI, 8.3 to 10.3) in the FP + BEV arm and 10.0 months (9.0 to 11.2) in the FP + BEV + OX arm (hazard ratio [HR], 0.84 [90.5% CI, 0.67 to 1.04]; one-sided = .086). The median overall survival was 21.3 months (18.7 to 24.3) in the FP + BEV arm and 19.7 months (15.5 to 25.5) in the FP + BEV + OX arm (HR, 1.05 [0.81 to 1.37]). The proportion of any grade ≥3 adverse events was higher in the FP + BEV + OX arm (52% 69%). There was one treatment-related death in the FP + BEV arm and three in the FP + BEV + OX arm.

CONCLUSION

No benefit of adding OX to FP + BEV as first-line treatment was demonstrated in older patients with MCRC. FP + BEV is recommended for this population.

摘要

目的

氟尿嘧啶（FP）和奥沙利铂（OX）联合贝伐珠单抗（BEV）的双联化疗是不可切除转移性结直肠癌（MCRC）的标准治疗方案。然而，对于年龄较大的患者（该人群标准治疗为 FP+BEV），添加 OX 对 FP+BEV 的疗效尚不清楚。我们旨在证实对于该人群添加 OX 对 FP+BEV 的优越性。

方法

这是一项在日本 42 家机构进行的开放标签、随机、III 期临床试验。招募年龄在 70-74 岁、东部肿瘤协作组体能状态（ECOG-PS）为 2 级和 75 岁及以上、ECOG-PS 为 0-2 级的不可切除 MCRC 患者，按 1:1 比例随机分配至 FP+BEV 组或 OX 加用（FP+BEV+OX）组。氟尿嘧啶+左亚叶酸钙或卡培他滨在入组前被指定。主要终点为无进展生存期（PFS）。该研究在日本临床试验注册中心（注册号：jRCTs031180145）注册。

结果

2012 年 9 月至 2019 年 3 月，251 例患者被随机分配至 FP+BEV 组（n=125）和 FP+BEV+OX 组（n=126）。两组的中位年龄分别为 80 岁和 79 岁。FP+BEV 组和 FP+BEV+OX 组的中位 PFS 分别为 9.4 个月（95%CI，8.3 至 10.3）和 10.0 个月（9.0 至 11.2）（HR，0.84 [90.5%CI，0.67 至 1.04]；单侧 =.086）。FP+BEV 组和 FP+BEV+OX 组的中位总生存期分别为 21.3 个月（18.7 至 24.3）和 19.7 个月（15.5 至 25.5）（HR，1.05 [0.81 至 1.37]）。FP+BEV+OX 组任何等级≥3 级不良事件的比例更高（52% 69%）。FP+BEV 组有 1 例与治疗相关的死亡，FP+BEV+OX 组有 3 例。