PEAK: A Randomized, Multicenter Phase II Study of Panitumumab Plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer
PEAK: A Randomized, Multicenter Phase II Study of Panitumumab Plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer
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DOI：
10.1200/jco.2013.53.2473
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发表时间：
2014-07-20
影响因子：
45.3
通讯作者：
Go, William Y.
中科院分区：
文献类型：
--
作者：
Schwartzberg, Lee S.;Rivera, Fernando;Go, William Y.
目的评价帕尼单抗联合改良氟尿嘧啶、亚叶酸和奥沙利铂（mFOLFOX 6）或贝伐单抗联合mFOLFOX 6治疗既往未经治疗的野生型（WT）KRAS外显子2（密码子12和13）转移性结直肠癌（mCRC）患者的疗效。一个预先设定的次要目的是评估扩展RAS分析的治疗效果，包括KRAS和NRAS.Patients和方法的外显子2，3和4与WT KRAS外显子2肿瘤患者被随机分配在一比一的比例帕尼单抗加mFOLFOX 6或贝伐单抗加mFOLFOX 6。主要终点是无进展生存期（PFS），次要终点包括总生存期（OS）和safety.Results随机分配的285例患者中，278例接受治疗。在WT KRAS外显子2意向治疗组中，两组的PFS相似（风险比[HR]，0.87; 95% CI，0.65 - 1.17; P = 0.353）。帕尼单抗组和贝伐单抗组的中位OS分别为34.2和24.3个月（HR，0.62; 95% CI，0.44 - 0.89; P = 0.009）。在WT RAS亚组（KRAS和NRAS的WT外显子2、3和4）中，PFS支持帕尼单抗组（HR，0. 65; 95% CI，0. 44 - 0. 96; P = 0. 029）。帕尼单抗和贝伐珠单抗组的中位OS分别为41.3和28.9个月（HR，0.63; 95% CI，0.39 - 1.02; P = 0.058）。结论在WT KRAS外显子2肿瘤患者中，帕尼单抗联合mFOLFOX 6治疗与贝伐单抗相比，PFS相似，OS改善。WT RAS肿瘤患者似乎经历了抗表皮生长因子受体治疗的更多临床获益。(C)2014年美国临床肿瘤学会
Purpose To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS.Patients and Methods Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety.Results Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms.Conclusion PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy. (C) 2014 by American Society of Clinical Oncology