ModifiedFOLFOXIRIWith or Without Cetuximab as Conversion Therapy in Patients withRAS/BRAFWild-TypeUnresectable Liver Metastases Colorectal Cancer: TheFOCULMMulticenter PhaseIITrial
ModifiedFOLFOXIRIWith or Without Cetuximab as Conversion Therapy in Patients withRAS/BRAFWild-TypeUnresectable Liver Metastases Colorectal Cancer: TheFOCULMMulticenter PhaseIITrial
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DOI：
10.1634/theoncologist.2020-0563
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发表时间：
2020-09-03
期刊：
影响因子：
5.8
通讯作者：
Deng, Yanhong
中科院分区：
文献类型：
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作者：
Hu, Huabin;Wang, Kun;Deng, Yanhong
目的本试验评价了在改良FOLFOXIRI方案（mFOLFOXIRI方案：5-氟尿嘧啶/亚叶酸、奥沙利铂、伊立替康）基础上加用西妥昔单抗作为转换治疗的一项两组、非随机、多中心、II期临床试验，治疗的患者为最初技术上不可切除的结直肠肝局限性转移瘤（CLM）和BRAF/RAS野生型。患者和方法患者入组接受西妥昔单抗（500 mg/m2）联合mFOLFOXIRI（奥沙利铂85 mg/m2，伊立替康165 mg/m2，亚叶酸400 mg/m2，5-氟尿嘧啶2,800 mg/m2，46小时输注，每2周一次）（西妥昔单抗组）或相同方案的单用mFOLFOXIRI（对照组），比例为2：1。主要终点是达到无疾病证据（NED）的比率。次要终点包括切除率、客观缓解率（ORR）、生存率和安全性。结果2014年2月至2019年7月，中国6家中心共登记了117例患者进行筛查，其中101例入组（西妥昔单抗组67例，对照组34例）。西妥昔单抗组的NED发生率为70.1%，对照组为41.2%（差异29.0%; 95%置信区间[CI]，9.1%-48.8%;p= 0.005）。与对照组相比，西妥昔单抗组患者的ORR有所改善（95.5% vs. 76.5%;差异19.1%; 95% CI，17.4%-36.4%;p= 0.010）。无进展生存期和总生存期显示出有利于西妥昔单抗组的趋势。两组中3级和4级不良事件的发生率相似。结论mFOLFOXIRI联合西妥昔单抗可提高NED的发生率。这种组合可能是一种选择转换方案的分子选择患者最初技术上无法切除的CLM。实践意义本试验评价了在改良FOLFOXIRI基础上加用西妥昔单抗作为转换治疗的II期临床试验，患者为最初技术上不可切除的结直肠肝局限性转移和BRAF/RAS野生型患者。西妥昔单抗联合改良FOLFOXIRI组和改良FOLFOXIRI组的无疾病证据发生率分别为70.1%和41.2%。与改良FOLFOXIRI组相比，西妥昔单抗组的客观缓解率、总生存期和无进展生存期均有所改善。在改良FOLFOXIRI方案中添加西妥昔单抗增加了无疾病证据的发生率，该联合方案可作为分子筛选的最初技术上不可切除的结直肠肝局限性转移患者的转换方案选择。
Purpose 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) andBRAF/RASwild-type. Patients and Methods Patients were enrolled to receive cetuximab (500 mg/m(2)) plus mFOLFOXIRI (oxaliplatin 85 mg/m(2), irinotecan 165 mg/m(2), folinic acid 400 mg/m(2), 5-fluorouracil 2,800 mg/m(2)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. Results 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. Conclusion 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. Implications for Practice 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 andBRAF/RASwild-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.