Kate Shruti, Chougule Anuradha, Joshi Amit, Noronha Vanita, Patil Vijay, Dusane Rohit, Solanki Leena, Tiwrekar Priyanka, Trivedi Vaishakhi, Prabhash Kumar
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India,
Department of Molecular Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
Lung Cancer (Auckl). 2019 Jan 29;10:1-10. doi: 10.2147/LCTT.S181406. eCollection 2019.
The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients.
We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan-Meier method and compared between groups using log-rank test.
Out of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8-8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4-28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1-21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2-37.0, =0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2-41.2, =0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations.
Uncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.
新诊断的晚期非小细胞肺癌（NSCLC）患者中不常见的表皮生长因子受体（EGFR）突变的意义尚不完全清楚。我们旨在分析这些患者的人口统计学特征、预后及治疗特点。
我们回顾性调查了2013年至2017年在我们中心接受EGFR检测的5738例晚期NSCLC患者，检测采用实时PCR平台上的内部引物探针。描述性数据从电子病历中收集。采用Kaplan-Meier法计算生存曲线，并使用对数秩检验进行组间比较。
在1260例EGFR突变阳性患者中，83例（6.58%）单独或多种组合存在不常见突变。不常见突变在男性、从不吸烟者和腺癌中更常见。总体而言，外显子18 G719X、外显子20插入、外显子20 T790M、外显子20 S768I和外显子21（L858R/L861Q）分别出现在9.6%、19.3%、12%、3.6%和3.6%的患者中。50.6%的患者存在双重突变阳性。根据酪氨酸激酶抑制剂（TKI）敏感性对患者进行分类时，发现大多数患者同时存在TKI敏感和不敏感突变。中位随访时间为13个月。5例患者失访。一线治疗的中位无进展生存期为6.7个月（95%置信区间：4.8 - 8.5）。在疾病过程中接受TKI治疗的患者的中位总生存期（OS）为20.2个月（95%置信区间：11.4 - 28.9）。整个队列的中位总生存期（mOS）为15.8个月（95%置信区间：10.1 - 21.5）。在所有不常见突变中，双重突变患者的情况较好，mOS时间为22.6个月（95%置信区间：8.2 - 37.0，P = 0.005）。据观察，与TKI敏感和TKI不敏感的EGFR突变相比，TKI敏感/TKI不敏感双重突变的OS为28.2个月（95%置信区间：15.2 - 41.2，P = 0.039），具有优势。
不常见的EGFR突变构成一个异质性群体，因此，更深入了解每个亚组以确定最佳治疗方法势在必行。
