Medical Oncology Department, Catalan Institute of Oncology and Applied Research Group in Oncology (B-ARGO), Badalona, Spain; Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.
Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Clin Lung Cancer. 2020 Sep;21(5):428-436.e2. doi: 10.1016/j.cllc.2020.04.011. Epub 2020 Apr 25.
Uncommon epidermal growth factor receptor (EGFR) mutations (u-EGFRm) are a heterogeneous group of molecular alterations and have also been reported as comutations with other EGFR mutations (complex mutations) in non-small-cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, and we examined its efficacy in Spanish clinical practice.
Data of 67 patients with advanced NSCLC with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. u-EGFRm were analyzed as complex mutations (group A), EGFR exon 20 insertions (ins20; group B), or single mutations (group C). Efficacy was evaluated in terms of overall survival (OS) and tumor response.
Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q. No differences in clinical characteristics were found between groups A (n = 20), B (n = 23), and C (n = 24). Afatinib was administered as first-line therapy in 80% of patients. Median time of receipt of therapy was 4.2 months (range, 2.0-12.9 months). Median OS for the entire cohort was 19.9 months (95% confidence interval, 9.7, 30.1). Hazard ratios for OS were 0.26 (95% confidence interval, 0.10, 0.71; P = .008) and 0.40 (95% confidence interval, 0.17, 0.95; P = .037) for groups A and C compared to B, respectively. Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P < .001 and .008, respectively).
In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.
罕见的表皮生长因子受体（EGFR）突变（u-EGFRm）是一组异质性的分子改变，也有报道称在非小细胞肺癌（NSCLC）中与其他 EGFR 突变（复合突变）共存。阿法替尼对一些 u-EGFRm 具有活性，我们研究了其在西班牙临床实践中的疗效。
对 2012 年至 2017 年间，23 家西班牙医疗机构的 67 例接受阿法替尼治疗的晚期 NSCLC 伴 u-EGFRm 的患者的数据进行了回顾性分析。u-EGFRm 分析为复杂突变（A 组）、EGFR 外显子 20 插入（ins20；B 组）或单突变（C 组）。根据总生存期（OS）和肿瘤反应评估疗效。
A 组复杂的 u-EGFRm 由 G719X+E709F、G719X+S768I、G719X+L861Q、L858R+T790M、L858R+S768I、L858R+S765I、del19+S768I、del19+L747S 或 R776C+L861Q 双重突变组成。A 组（n=20）、B 组（n=23）和 C 组（n=24）患者的临床特征无差异。80%的患者接受阿法替尼作为一线治疗。中位治疗时间为 4.2 个月（范围 2.0-12.9 个月）。整个队列的中位 OS 为 19.9 个月（95%置信区间，9.7-30.1）。与 B 组相比，A 组和 C 组的 OS 风险比分别为 0.26（95%置信区间，0.10-0.71；P=0.008）和 0.40（95%置信区间，0.17-0.95；P=0.037）。与 B 组相比，A 组（70%）和 C 组（54%）的反应明显更高（两两比较 P<.001 和 P<.008）。
在临床实践中，阿法替尼对伴有 u-EGFRm 的 NSCLC 患者有效，尤其是在复杂和单突变患者中。对于 ins20 患者，需要进一步的治疗策略，因为他们是一个亚组 u-EGFRm，接受阿法替尼治疗的临床获益较低。
