Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Natl Cancer Inst. 2021 Nov 2;113(11):1561-1569. doi: 10.1093/jnci/djab069.
EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC.
In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided.
EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002).
Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies.
表皮生长因子受体（EGFR）扩增发生在约 1%的转移性结直肠癌（mCRC）患者中，但不作为接受抗 EGFR 单克隆抗体治疗患者的预后或预测生物标志物进行常规检测。在此，我们旨在描述 EGFR 扩增 mCRC 的临床和分子特征。
在这项多中心队列研究中，我们比较了 62 例 EGFR 扩增与 1459 例 EGFR 非扩增 mCRC 患者的临床数据，以及 35 例 EGFR 扩增与 439 例 RAS/BRAF 野生型和微卫星稳定（MSS）肿瘤样本的综合基因组数据。所有统计检验均为双侧检验。
EGFR 扩增与左原发性肿瘤侧别和 RAS/BRAF 野生型状态具有统计学显著相关性。所有 EGFR 扩增肿瘤均为 MSS 和 HER2 非扩增。总体而言，与 EGFR 非扩增、RAS/BRAF 野生型 MSS 队列相比，EGFR 扩增样本的基因组改变比例中位数更高。EGFR 扩增肿瘤患者的总生存期（OS）更长（中位 OS = 71.3 个月，95%置信区间[CI] = 50.7 至无进展[NA]），而非 EGFR 扩增肿瘤患者的 OS 更短（24.0 个月；95%CI = 22.8 至 25.6；风险比[HR] = 0.30，95%CI = 0.20 至 0.44；P <.001；调整 HR = 0.46，95%CI = 0.30 至 0.69；P <.001）。在接受基于抗 EGFR 治疗的 RAS/BRAF 野生型 mCRC 患者亚组中，EGFR 扩增再次与更好的 OS 相关（中位 OS = 54.0 个月，95%CI = 35.2 至 NA，与 29.1 个月，95%CI = 27.0 至 31.9 相比；HR = 0.46，95%CI = 0.28 至 0.76；P =.002）。
EGFR 扩增 mCRC 患者代表了一个生物学定义的亚组，值得进行专门的临床试验，采用新的、更有效的 EGFR 靶向策略，而不仅仅是单克隆抗体。
