Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.
Cancer. 2012 Mar 15;118(6):1523-32. doi: 10.1002/cncr.26460. Epub 2011 Aug 25.
Antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MoAbs) are indicated for the treatment of metastatic colorectal cancer patients, but some scientific issues concerning their efficacy are currently unsolved.
A literature-based meta-analysis was conducted. Hazard ratios (HRs) were extracted from randomized trials for progression-free survival (PFS) and overall survival (OS); the event-based risk ratio was derived for response. Sensitivity analyses to look for interactions according to KRAS status and chemotherapy association regimens were performed.
Eight trials (6609 patients) were identified. A significant interaction according to KRAS status was found for PFS (wild type vs mutant, P = .001) and response rate (wild type vs mutant, P < .0001). The addition of an anti-EGFR MoAb to first-line chemotherapy increased PFS in the KRAS wild-type population (HR, 0.91; 95% confidence interval [CI], 0.84-0.99; P = .03), and had a detrimental effect in the KRAS mutant population (HR, 1.13; 95% CI, 1.03-1.25; P = .013). A significant increase in the probability of achieving a response was evident in KRAS wild-type patients (relative risk, 1.17; 95% CI, 1.04-1.33; P = .011). In this population, the interaction in response rate according to adopted chemotherapy favored irinotecan-containing regimens (P = .01), and at meta-regression analysis the relative increase in response rate was significantly related to PFS (P = .00001) and OS (P = .00193) benefit.
The addition of an anti-EGFR MoAb to first-line chemotherapy produces a clear benefit in response rate. This advantage is restricted to KRAS wild-type patients and translates into a small benefit in PFS. At present, irinotecan-based backbone chemotherapy could be a preferable option. The correlation between activity and survival parameters corroborates the hypothesis that anti-EGFR MoAbs might be more suitable for patients needing tumoral shrinkage.
抗表皮生长因子受体（anti-EGFR）单克隆抗体（MoAbs）被用于治疗转移性结直肠癌患者，但它们的疗效仍存在一些尚未解决的科学问题。
进行了基于文献的荟萃分析。从无进展生存期（PFS）和总生存期（OS）的随机试验中提取风险比（HRs）；根据事件的风险比得出反应率。根据 KRAS 状态和化疗联合方案进行了敏感性分析，以寻找相互作用。
确定了 8 项试验（6609 例患者）。发现 PFS（野生型与突变型，P=0.001）和反应率（野生型与突变型，P<0.0001）存在与 KRAS 状态相关的显著交互作用。在 KRAS 野生型人群中，将抗 EGFR MoAb 添加到一线化疗中可增加 PFS（HR，0.91；95%置信区间[CI]，0.84-0.99；P=0.03），而在 KRAS 突变型人群中则产生不利影响（HR，1.13；95%CI，1.03-1.25；P=0.013）。在 KRAS 野生型患者中，明显提高了获得反应的概率（相对风险，1.17；95%CI，1.04-1.33；P=0.011）。在该人群中，根据采用的化疗方案，反应率的交互作用有利于伊立替康类方案（P=0.01），而在荟萃回归分析中，反应率的相对增加与 PFS（P=0.00001）和 OS（P=0.00193）获益显著相关。
将抗 EGFR MoAb 添加到一线化疗中可显著提高反应率。这种优势仅限于 KRAS 野生型患者，并且在 PFS 中转化为较小的获益。目前，基于伊立替康的基础化疗可能是一种更好的选择。活性和生存参数之间的相关性证实了这样一种假设，即抗 EGFR MoAbs 可能更适合需要肿瘤缩小的患者。
