Introduction: Necitumumab is a monoclonal antibody targeting EGFR. In the SQUIRE trial, the addition of necitumumab to chemotherapy for squamous cell lung cancer significantly improved overall survival (OS) (hazard ratio [HR] = 0.84); in a post hoc analysis, EGFR copy number gain determined by fluorescence in situ hybridization (FISH) showed a trend toward improved OS (HR = 0.70) and progression‐free survival (PFS) (HR = 0.71) with the addition of necitumumab. We present the analysis of granular EGFR FISH data from SQUIRE to examine the potential predictive role of high polysomy and gene amplification, as both were included in the FISH‐positive category. Methods: Available specimens from SQUIRE underwent FISH analysis in a central laboratory, and each sample was evaluated by using the Colorado EGFR scoring criteria. The correlation of granular FISH parameters with clinical outcomes was assessed. Results: Samples were available for 557 of 1093 patients; 208 patients (37.3%) were FISH‐positive, including 167 (30.0%) with high polysomy and 41 (7.4%) with gene amplification. In patients with high polysomy, the addition of necitumumab resulted in a statistically significant increase in PFS (6.08 versus 5.13 months [p = 0.044]) and nonstatistically significant increase in OS (12.6 versus 9.5 months [p = 0.133]); among patients with gene amplification, the addition of necitumumab did not significantly improve PFS (7.4 versus 5.6 months; [p = 0.334]) but did improve OS (14.8 versus 7.6 months; [p = 0.033]). Conclusions: EGFR copy number gain by FISH might have a role as a predictive biomarker for necitumumab in squamous cell lung cancer. In our opinion, these data encourage further studies to prospectively evaluate this potential biomarker.

中文翻译：

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FISH 的 EGFR 基因拷贝数可能预测 necitumumab 在鳞状肺癌中的结果：来自 SQUIRE 研究的分析

简介： Necitumumab 是一种靶向 EGFR 的单克隆抗体。在 SQUIRE 试验中，在鳞状细胞肺癌化疗中加入 necitumumab 显着提高了总生存期 (OS)（风险比 [HR] = 0.84）；在事后分析中，通过荧光原位杂交 (FISH) 确定的 EGFR 拷贝数增加显示出通过添加 necitumumab 改善 OS (HR = 0.70) 和无进展生存 (PFS) (HR = 0.71) 的趋势。我们展示了来自 SQUIRE 的粒度 EGFR FISH 数据的分析，以检查高多体性和基因扩增的潜在预测作用，因为两者都包含在 FISH 阳性类别中。方法：来自 SQUIRE 的可用标本在中心实验室进行 FISH 分析，并使用科罗拉多州 EGFR 评分标准对每个样本进行评估。评估了颗粒 FISH 参数与临床结果的相关性。结果： 1093 名患者中有 557 名样本可用；208 名患者 (37.3%) 为 FISH 阳性，其中 167 名 (30.0%) 为高多体性，41 名 (7.4%) 为基因扩增。在高多体性患者中，添加 necitumumab 导致 PFS 有统计学显着增加（6.08 对 5.13 个月 [p = 0.044]）和 OS 非统计学显着增加（12.6 对 9.5 个月 [p = 0.133]）；在基因扩增的患者中，添加 necitumumab 并没有显着改善 PFS（7.4 与 5.6 个月；[p = 0.334]），但确实改善了 OS（14.8 与 7.6 个月；[p = 0.033]）。结论：通过 FISH 获得的 EGFR 拷贝数增加可能作为 necitumumab 在鳞状细胞肺癌中的预测生物标志物。在我们看来，