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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.

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。

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