晚期鳞状细胞肺癌中针对表皮生长因子受体的单克隆抗体反应的预测生物标志物。
Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer.
机构信息
Department of Internal Medicine, Rush University Medical Center, Chicago, USA.
Department of Hematology and Oncology, UC Davis Comprehensive Cancer Center, Sacramento, USA.
出版信息
Ann Oncol. 2018 Aug 1;29(8):1701-1709. doi: 10.1093/annonc/mdy196.
BACKGROUND
Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs.
DESIGN
Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized.
RESULTS
Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents.
CONCLUSIONS
Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.
背景
表皮生长因子受体（EGFR）的表达上调和异常激活存在于肺癌中，使其成为非小细胞肺癌（NSCLC）的一个相关靶点。针对鳞状细胞肺癌（SqCLC）患者，使用抗 EGFR 单克隆抗体（mAb）治疗与总生存期的适度改善相关，这些患者对有效治疗方案存在显著未满足的需求。虽然有证据表明，使用 EGFR 基因拷贝数、EGFR 突变和 EGFR 蛋白表达作为生物标志物有助于选择对治疗有反应的患者，但考虑到包括 EGFR mAb 在内的联合治疗中对反应的生物标志物也很重要。
设计
在文献中搜索了针对 EGFR 的 mAb 西妥昔单抗和耐昔妥珠单抗联合化疗、免疫治疗或抗血管生成治疗晚期 NSCLC，包括 SqCLC 的随机试验。总结了潜在生物标志物与结果之间的关联结果。
结果
来自 III 期临床试验的数据表明，肿瘤表达高水平 EGFR 蛋白（H 评分≥200）和/或 EGFR 基因拷贝数（例如，通过荧光原位杂交检测到≥40%的细胞具有≥4 个 EGFR 拷贝；在分析的≥10%细胞中存在基因扩增）的 NSCLC 患者，包括 SqCLC，从 EGFR 靶向 mAb 中获得更大的治疗益处。与免疫治疗联合使用时，EGFR mAb 的生物标志物数据有限，与抗血管生成剂联合使用时则没有。
结论
EGFR 靶向 mAb 联合化疗治疗与 NSCLC，包括 SqCLC，患者的更大临床获益相关，这些患者的肿瘤表达高水平的 EGFR 蛋白和/或具有增加的 EGFR 基因拷贝数。这些数据支持验证这些生物标志物的作用，以确定从 EGFR mAb 治疗中获益最大的患者。然而，关于与免疫治疗或抗血管生成剂联合使用的 EGFR 靶向 mAb 的生物标志物数据仍然有限。
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