Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2010 May 28;70(8):1059-78. doi: 10.2165/11205090-000000000-00000.
Panitumumab (Vectibix(R)) is a recombinant, fully human, IgG2 anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This article reviews the clinical efficacy of intravenous panitumumab in combination with chemotherapy in the first- and second-line treatment of metastatic colorectal cancer and as monotherapy in chemotherapy-refractory metastatic colorectal cancer, as well as summarizing its pharmacological properties and tolerability. Panitumumab is indicated for use in patients with wild-type rather than mutant KRAS tumours. The efficacy of intravenous panitumumab 6 mg/kg administered every 2 weeks was examined in randomized, open-label, multicentre, phase III trials in patients with metastatic colorectal cancer. When administered as first- or second-line treatment in combination with chemotherapy, panitumumab plus chemotherapy prolonged progression-free survival to a significantly greater extent than chemotherapy alone in patients with wild-type KRAS tumours; no significant between-group difference in overall survival was seen in the second-line treatment trial. In patients with mutant KRAS tumours, progression-free survival was significantly shorter with panitumumab plus oxaliplatin-based chemotherapy than with oxaliplatin-based chemotherapy alone in the first-line treatment trial, with no significant difference between patients receiving panitumumab plus irinotecan-based chemotherapy (FOLFIRI) and those receiving FOLFIRI alone in the second-line treatment trial. In chemotherapy-refractory patients with metastatic colorectal cancer, panitumumab monotherapy plus best supportive care prolonged progression-free survival to a significantly greater extent than best supportive care alone in both the overall population and in patients with wild-type KRAS tumours, but not in those with mutant KRAS tumours; there was no significant between-group difference in overall survival. Panitumumab has an acceptable tolerability profile when administered as monotherapy or in combination with chemotherapy. It is associated with the skin-related toxicities characteristic of EGFR inhibitors and appears to have a low risk of immunogenicity. In conclusion, in patients with wild-type KRAS tumours, panitumumab is a useful option in combination with chemotherapy for the first- and second-line treatment of metastatic colorectal cancer or as monotherapy for the treatment of chemotherapy-refractory metastatic colorectal cancer.
帕尼单抗(Vectibix(R))是一种重组的、完全人源化的 IgG2 抗表皮生长因子受体(EGFR)单克隆抗体。本文综述了静脉用帕尼单抗联合化疗治疗转移性结直肠癌一线和二线治疗以及化疗耐药转移性结直肠癌单药治疗的临床疗效,并总结了其药理学特性和耐受性。帕尼单抗适用于野生型而非突变型 KRAS 肿瘤患者。在转移性结直肠癌患者中进行的随机、开放标签、多中心、III 期试验中,评估了每 2 周静脉给予 6mg/kg 帕尼单抗的疗效。作为一线或二线治疗联合化疗时,与化疗相比,野生型 KRAS 肿瘤患者中帕尼单抗联合化疗显著延长了无进展生存期;二线治疗试验中未观察到总生存期的显著组间差异。在突变型 KRAS 肿瘤患者中,与单独接受奥沙利铂为基础的化疗相比,一线治疗试验中帕尼单抗联合奥沙利铂为基础的化疗显著缩短了无进展生存期,二线治疗试验中接受帕尼单抗联合伊立替康为基础的化疗(FOLFIRI)的患者与单独接受 FOLFIRI 的患者之间无显著差异。在化疗耐药的转移性结直肠癌患者中,与单独最佳支持治疗相比,帕尼单抗单药联合最佳支持治疗在总体人群和野生型 KRAS 肿瘤患者中显著延长了无进展生存期,但在突变型 KRAS 肿瘤患者中无显著差异;总生存期无显著组间差异。帕尼单抗单药或联合化疗时具有可接受的耐受性。它与 EGFR 抑制剂相关的皮肤毒性特征有关,似乎具有低免疫原性风险。总之,在野生型 KRAS 肿瘤患者中,帕尼单抗联合化疗是转移性结直肠癌一线和二线治疗的有效选择,或作为化疗耐药转移性结直肠癌的单药治疗。