Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China.
Oncologist. 2021 Jan;26(1):e90-e98. doi: 10.1634/theoncologist.2020-0563. Epub 2020 Sep 3.
This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type.
Patients were enrolled to receive cetuximab (500 mg/m ) plus mFOLFOXIRI (oxaliplatin 85 mg/m , irinotecan 165 mg/m , folinic acid 400 mg/m , 5-fluorouracil 2,800 mg/m 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety.
Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups.
Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM.
This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.
本试验评估了在 BRAF/RAS 野生型、初始技术上不可切除的结直肠癌肝转移（CLM）患者中，西妥昔单抗联合改良 FOLFOXIRI（mFOLFOXIRI：5-氟尿嘧啶/亚叶酸钙、奥沙利铂、伊立替康）作为转化治疗的效果。这是一项两组、非随机、多中心、二期临床试验。
本研究共纳入了 117 名患者，他们被分配到西妥昔单抗联合 mFOLFOXIRI（奥沙利铂 85mg/m²、伊立替康 165mg/m²、亚叶酸钙 400mg/m²、5-氟尿嘧啶 2800mg/m² 持续 46 小时输注，每 2 周一次）（西妥昔单抗组）或单纯 mFOLFOXIRI（对照组）治疗，分组比例为 2:1。主要终点是无疾病证据（NED）的发生率。次要终点包括切除率、客观缓解率（ORR）、总生存期和安全性。
2014 年 2 月至 2019 年 7 月，共有 6 家中国中心的 117 名患者接受了筛选，其中 101 名患者入组（西妥昔单抗组 67 例，对照组 34 例）。西妥昔单抗组的 NED 率为 70.1%，对照组为 41.2%（差异 29.0%；95%置信区间[CI]，9.1%-48.8%；p =.005）。西妥昔单抗组的 ORR（95.5%比 76.5%；差异 19.1%；95%CI，17.4%-36.4%；p =.010）优于对照组。无进展生存期和总生存期均显示出有利于西妥昔单抗组的趋势。两组的 3/4 级不良事件发生率相似。
西妥昔单抗联合 mFOLFOXIRI 提高了 NED 的发生率。这种联合方案可能是分子选择的初始技术上不可切除的 CLM 患者的转化治疗选择之一。
