Department of Laboratory and Transfusion Services and Department of Research, Rajiv Gandhi Cancer Institute & Research Centre, Rohini, Delhi-110085, India.
Department of Research, Rajiv Gandhi Cancer Institute & Research Centre, Rohini, Delhi-110085, India.
Cancer Treat Res Commun. 2021;28:100398. doi: 10.1016/j.ctarc.2021.100398. Epub 2021 May 13.
The predictive value of rare epidermal growth factor receptor gene (EGFR) mutations for non-small cell lung carcinoma (NSCLC) patients remain elusive. We evaluated the distribution, clinicopathological association, tyrosine kinase inhibitor (TKI) response, and outcome of NSCLC patients carrying uncommon EGFR aberrations in comparison to classical EGFR mutations.
Treatment naïve, advanced NSCLC cases tested by Next-Generation sequencing (NGS) method between 2015 and 2020 were included. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed.
A total of 237 tumor samples were sequenced. Among the sixty-nine (29%) EGFR mutated cases, 41 (59.4%) harbored classical mutation (37.7% Del19, 21.7% p.L858R). Non-classical aberrations included missense mutations in exon 18/20/21 (15.9%), EGFR amplification (8.7%), exon 20 insertions (7.2%), EGFR Variant III (4.3%), exon 18 indel (2.9%), exon 21 missense (2.9%) and exon 19 missense mutation (1.4%). These occurred as complex mutations in 16% of cases. Oral TKI was administered in 66.7% cases. The patients harboring non-classical variants had a lower ORR and DCR (23.1% and 61.5%) than those carrying a common mutation (57.6% and 84.8%). Collectively, compared to the patients with common EGFR mutations, the uncommon group showed early disease progression and had shorter overall survival.
NGS testing has the capacity to reveal a diverse spectrum of uncommon EGFR variants. Our study can contribute to the database of uncommon EGFR mutations with a positive influence on evidence-based care of advanced lung cancer patients with EGFR mutations.
非小细胞肺癌（NSCLC）患者罕见表皮生长因子受体基因（EGFR）突变的预测价值仍不清楚。我们评估了与经典 EGFR 突变相比，携带非典型 EGFR 异常的 NSCLC 患者的分布、临床病理相关性、酪氨酸激酶抑制剂（TKI）反应和结局。
纳入 2015 年至 2020 年间通过下一代测序（NGS）方法检测的未经治疗的晚期 NSCLC 病例。分析客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。
共对 237 个肿瘤样本进行了测序。在 69 例（29%）EGFR 突变病例中，41 例（59.4%）携带经典突变（37.7% Del19，21.7% p.L858R）。非典型异常包括外显子 18/20/21 的错义突变（15.9%）、EGFR 扩增（8.7%）、外显子 20 插入（7.2%）、EGFR 变体 III（4.3%）、外显子 18 缺失（2.9%）、外显子 21 错义突变（2.9%）和外显子 19 错义突变（1.4%）。这些在 16%的病例中发生为复杂突变。66.7%的病例给予口服 TKI 治疗。携带非典型变异的患者的 ORR 和 DCR（23.1%和 61.5%）低于携带常见突变的患者（57.6%和 84.8%）。总的来说，与携带常见 EGFR 突变的患者相比，不常见组疾病进展较早，总生存期较短。
NGS 检测具有揭示多种罕见 EGFR 变异的能力。我们的研究可以为罕见 EGFR 突变的数据库做出贡献，并对基于证据的 EGFR 突变晚期肺癌患者的治疗产生积极影响。
