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综述文章:帕尼单抗——一种用于治疗转移性结直肠癌的全人源抗表皮生长因子受体单克隆抗体

Review article: panitumumab--a fully human anti-EGFR monoclonal antibody for treatment of metastatic colorectal cancer.

作者信息

Peeters M, Balfour J, Arnold D

机构信息

Department of Hepatogastroenterology, Digestive Oncology Unit, University Hospital Ghent, Gent, Belgium.

出版信息

Aliment Pharmacol Ther. 2008 Aug 1;28(3):269-81. doi: 10.1111/j.1365-2036.2008.03717.x.

DOI:10.1111/j.1365-2036.2008.03717.x
PMID:19086328
Abstract

BACKGROUND

Panitumumab is a fully human monoclonal IgG2 antibody targeting the epidermal growth factor receptor (EGFR).

AIM

To review the efficacy of panitumumab in the treatment of metastatic colorectal cancer (mCRC).

METHODS

Available literature identified from PubMed and conference websites was reviewed.

RESULTS

In phase 2-3 studies, panitumumab monotherapy achieved objective response rates (ORRs) of 8-13% in relapsed/refractory EGFR-expressing mCRC. In a randomized phase 3 study (463 patients), panitumumab almost halved the risk of disease progression/death vs. a control group receiving only best supportive care (hazard ratio 0.54; 95% CI: 0.44-0.66; P < 0.0001). Objective response was achieved in 22/231 (10%) patients randomized to panitumumab--and also in 20/176 (11%) patients assigned to the control group who received panitumumab in a separate crossover protocol after disease progression. Response was confined to patients with tumours harbouring wild-type KRAS (ORR approximately equal to 20%). Panitumumab is also being evaluated in earlier lines of treatment. Panitumumab monotherapy is generally well tolerated; the most common toxicities are skin toxicity (approximately equal to 90%) and diarrhoea (<30%). Development of anti-panitumumab antibodies (0.3% by ELISA) and grade 3-4 infusion reactions (<1%) are rare.

CONCLUSION

Panitumumab is an effective monotherapy option for patients with relapsed/refractory EGFR-expressing mCRC harbouring wild-type KRAS.

摘要

背景

帕尼单抗是一种靶向表皮生长因子受体(EGFR)的全人源单克隆IgG2抗体。

目的

综述帕尼单抗治疗转移性结直肠癌(mCRC)的疗效。

方法

回顾从PubMed和会议网站检索到的相关文献。

结果

在2-3期研究中,帕尼单抗单药治疗在复发/难治性EGFR表达阳性的mCRC患者中实现了8%-13%的客观缓解率(ORR)。在一项随机3期研究(463例患者)中,与仅接受最佳支持治疗的对照组相比,帕尼单抗使疾病进展/死亡风险几乎减半(风险比0.54;95%CI:0.44-0.66;P<0.0001)。随机接受帕尼单抗治疗的22/231例(10%)患者以及疾病进展后在单独交叉方案中接受帕尼单抗治疗的对照组20/176例(11%)患者获得了客观缓解。缓解仅限于携带野生型KRAS肿瘤的患者(ORR约为20%)。帕尼单抗也正在早期治疗方案中进行评估。帕尼单抗单药治疗一般耐受性良好;最常见的毒性是皮肤毒性(约90%)和腹泻(<30%)。抗帕尼单抗抗体的产生(ELISA法检测为0.3%)和3-4级输注反应(<1%)很少见。

结论

对于复发/难治性、EGFR表达阳性、携带野生型KRAS的mCRC患者,帕尼单抗是一种有效的单药治疗选择。

相似文献

1
Review article: panitumumab--a fully human anti-EGFR monoclonal antibody for treatment of metastatic colorectal cancer.综述文章:帕尼单抗——一种用于治疗转移性结直肠癌的全人源抗表皮生长因子受体单克隆抗体
Aliment Pharmacol Ther. 2008 Aug 1;28(3):269-81. doi: 10.1111/j.1365-2036.2008.03717.x.
2
Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study.随机、III 期临床试验:帕尼单抗联合氟尿嘧啶、亚叶酸钙和奥沙利铂(FOLFOX4)对比 FOLFOX4 一线治疗未经治疗的转移性结直肠癌患者:PRIME 研究。
J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
3
Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer.一项比较帕尼单抗联合氟尿嘧啶、亚叶酸钙和伊立替康(FOLFIRI)与单独 FOLFIRI 二线治疗转移性结直肠癌患者的随机 III 期研究。
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4
The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status.帕尼单抗联合 FOLFIRI 或伊立替康二线治疗转移性结直肠癌的疗效和安全性:根据 KRAS 状态的 STEPP(帕尼单抗皮肤毒性评估方案)的二次分析。
Clin Colorectal Cancer. 2011 Dec;10(4):333-9. doi: 10.1016/j.clcc.2011.06.004. Epub 2011 Oct 14.
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Panitumumab in patients with KRAS wild-type colorectal cancer after progression on cetuximab.帕尼单抗治疗西妥昔单抗治疗后进展的 KRAS 野生型结直肠癌患者。
Oncologist. 2012;17(1):14. doi: 10.1634/theoncologist.2011-0452. Epub 2011 Dec 30.
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Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review.单克隆抗体在转移性结直肠癌治疗中的应用:综述。
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Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer.随机、Ⅱ期研究:胰岛素样生长因子-1 受体抑制剂 IMC-A12 联合或不联合西妥昔单抗治疗西妥昔单抗或帕尼单抗耐药的转移性结直肠癌患者。
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Integration of panitumumab into the treatment of colorectal cancer.帕尼单抗在结直肠癌治疗中的应用。
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Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.野生型KRAS是帕尼单抗对转移性结直肠癌患者疗效所必需的。
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Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab.转移性结直肠癌患者中 KRAS 密码子 12 和 13 突变等位基因:作为 panitumumab 反应的预后和预测生物标志物的评估。
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