Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, Korea.
Invest New Drugs. 2012 Aug;30(4):1607-13. doi: 10.1007/s10637-011-9703-8. Epub 2011 Jun 25.
Cetuximab plus irinotecan has been shown to be effective in metastatic colorectal cancer (mCRC) patients with wild-type (WT) KRAS and positive EGFR expressions (EGFR+). Retrospective analysis revealed that the efficacy of cetuximab was similar in mCRC patients negative (EGFR-) and positive for EGFR. However, the efficacy of cetuximab has not been assessed prospectively in EGFR- mCRC patients.
This was a prospective, multicenter phase II study assessed the efficacy and safety of biweekly cetuximab (500 mg/m(2)) and irinotecan (150-180 mg/m(2)) in patients with histologically proven adenocarcinoma with WT-KRAS and measurable lesion(s), either EGFR + or EGFR-, determined immunohistochemically, who failed first-line irinotecan-containing chemotherapy. The primary endpoint was response rate (RR), and the secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS).
Forty patients were enrolled; 20 EGFR + and 20 EGFR-; their baseline characteristics were balanced. The overall RR was 45% (18/40, 95% CI 29.6-60.4), 55% (11/20) in EGFR + and 35% (7/20) in EGFR- patients. Median PFS was 7.1 months (95% CI 4.8-9.4), 8.3 months in EGFR + and 4.9 months in EGFR- patients. Median OS was 18.5 months (95% CI 15.2-21.8), 17.2 months in EGFR + and 18.5 months in EGFR- patients. Grade 3 or 4 toxicities included neutropenia in 5 patients (12.5%) and febrile neutropenia/skin rash/asthenia in 2 (5%).
Biweekly cetuximab plus irinotecan as second-line treatment showed significant anti-tumor activity in patients with irinotecan-refractory mCRC and WT-KRAS regardless of EGFR expression status.
西妥昔单抗联合伊立替康已被证明在野生型（WT）KRAS 和阳性 EGFR 表达（EGFR+）的转移性结直肠癌（mCRC）患者中有效。回顾性分析显示，西妥昔单抗在 mCRC 患者 EGFR-和 EGFR+中的疗效相似。然而，西妥昔单抗在 EGFR- mCRC 患者中的疗效尚未前瞻性评估。
这是一项前瞻性、多中心 II 期研究，评估了组织学证实为腺癌且 WT-KRAS 阳性、有可测量病变的患者二线接受每两周一次西妥昔单抗（500mg/m2）和伊立替康（150-180mg/m2）治疗的疗效和安全性，这些患者在接受含伊立替康的一线化疗后进展，免疫组织化学法检测为 EGFR+或 EGFR-。主要终点为缓解率（RR），次要终点包括安全性、无进展生存期（PFS）和总生存期（OS）。
共纳入 40 例患者；20 例 EGFR+，20 例 EGFR-；他们的基线特征均衡。总体 RR 为 45%（18/40，95%CI 29.6-60.4），EGFR+患者为 55%（11/20），EGFR-患者为 35%（7/20）。中位 PFS 为 7.1 个月（95%CI 4.8-9.4），EGFR+患者为 8.3 个月，EGFR-患者为 4.9 个月。中位 OS 为 18.5 个月（95%CI 15.2-21.8），EGFR+患者为 17.2 个月，EGFR-患者为 18.5 个月。3 或 4 级毒性包括 5 例（12.5%）中性粒细胞减少症和 2 例（5%）发热性中性粒细胞减少症/皮疹/乏力。
二线使用西妥昔单抗联合伊立替康治疗对伊立替康耐药的 WT-KRAS 阳性 mCRC 患者具有显著的抗肿瘤活性，无论 EGFR 表达状态如何。
