A Randomized Phase IIIB Trial of Chemotherapy, Bevacizumab, and Panitumumab Compared With Chemotherapy and Bevacizumab Alone for Metastatic Colorectal Cancer
A Randomized Phase IIIB Trial of Chemotherapy, Bevacizumab, and Panitumumab Compared With Chemotherapy and Bevacizumab Alone for Metastatic Colorectal Cancer
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DOI：
10.1200/jco.2008.19.8135
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发表时间：
2009-02-10
影响因子：
45.3
通讯作者：
Amado, Rafael G.
中科院分区：
文献类型：
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作者：
Hecht, J. Randolph;Mitchell, Edith;Amado, Rafael G.
帕尼单抗是一种靶向表皮生长因子受体的全人源抗体，对转移性结直肠癌（mCRC）患者具有活性。这项试验评估帕尼单抗添加到贝伐单抗和化疗（奥沙利铂和伊立替康为基础）作为一线治疗mCRC.Patients和MethodsPatients被随机分配在每个化疗队列贝伐单抗和化疗或不帕尼单抗6毫克/公斤，每2周。主要终点是奥沙利铂队列中的无进展生存期（PFS）。每12周进行一次肿瘤评估和审查central.ResultsA共823和230例患者被随机分配到奥沙利铂和伊立替康队列，分别。在对812例奥沙利铂患者进行计划的中期分析后，帕尼单抗停药，帕尼单抗组的疗效较差。在最终分析中，帕尼单抗组和对照组的中位PFS分别为10.0和11.4个月（HR，1.27; 95% CI，1.06 - 1.52）;帕尼单抗组和对照组的中位生存期分别为19.4个月和24.5个月。奥沙利铂队列（帕尼单抗与对照组）中的3/4级不良事件包括皮肤毒性（36%与1%）、腹泻（24%与13%）、感染（19%与10%）和肺栓塞（6%与4%）。在伊立替康队列的帕尼单抗组中观察到毒性增加，但无疗效改善的证据。KRAS分析显示，帕尼单抗臂在野生型和突变groups.ConclusionThe除了帕尼单抗贝伐单抗和奥沙利铂或伊立替康为基础的化疗的毒性增加和PFS下降的结果。在临床实践中，不建议将这些组合用于治疗mCRC。
PurposePanitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC.Patients and MethodsPatients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks. The primary end point was progression-free survival (PFS) within the oxaliplatin cohort. Tumor assessments were performed every 12 weeks and reviewed centrally.ResultsA total of 823 and 230 patients were randomly assigned to the oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued after a planned interim analysis of 812 oxaliplatin patients showed worse efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and 11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% Cl, 1.06 to 1.52); median survival was 19.4 months and 24.5 months for the panitumumab and control arms, respectively. Grade 3/4 adverse events in the oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%), diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%). Increased toxicity without evidence of improved efficacy was observed in the panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes for the panitumumab arm in both wild-type and mutant groups.ConclusionThe addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These combinations are not recommended for the treatment of mCRC in clinical practice.