Department of Internal Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, California.
Global Evidence and Outcomes Oncology, Takeda Development Center Americas, Inc., Lexington, Massachusetts.
J Thorac Oncol. 2023 Jun;18(6):744-754. doi: 10.1016/j.jtho.2023.01.086. Epub 2023 Feb 3.
EGFR exon 20 insertion (ex20ins) mutations represent 5% to 10% of EGFR mutations in NSCLC. Identifying patients with EGFR ex20ins is challenging owing to the limited coverage of polymerase chain reaction (PCR) assays and the relatively recent use of next-generation sequencing (NGS). This study analyzes the spectrum of EGFR ex20ins variants in a large patient population from a global clinical trial and several real-world cohorts and the ability of PCR kits to identify these alterations.
We conducted this retrospective analysis in patients with NSCLC who underwent NGS or other sequencing testing and had a known EGFR ex20ins mutation. Patients were gathered from a clinical trial (NCT02716116), a chart review study in Germany, and the LC-SCRUM-Japan, GENIE, and U.S. COTA databases. Proportions of patients with ex20ins variants that could have been detected by six commercially available and widely used PCR kits were calculated in each data set.
Overall, 636 patients with NSCLC harboring EGFR ex20ins mutations were included in this analysis and 104 unique EGFR ex20ins variants were identified across the data sources. The proportion of patients whose ex20ins could have been detected by any PCR test alone ranged from 11.8% to 58.9% across the data sources.
Our findings suggest that the PCR tests evaluated would have missed more than 40% of patients with NSCLC harboring EGFR ex20ins mutations. NGS-based genetic testing is preferable than standard PCR assays and can substantially improve the identification of the diverse profile of EGFR ex20ins variants in NSCLC.
EGFR 外显子 20 插入（ex20ins）突变占非小细胞肺癌（NSCLC）中 EGFR 突变的 5%至 10%。由于聚合酶链反应（PCR）检测的覆盖范围有限以及新一代测序（NGS）的相对较新应用，识别 EGFR ex20ins 患者具有挑战性。本研究分析了来自全球临床试验和几个真实世界队列的大量患者人群中 EGFR ex20ins 变体的谱，以及 PCR 试剂盒识别这些改变的能力。
我们对接受了 NGS 或其他测序检测且已知 EGFR ex20ins 突变的 NSCLC 患者进行了这项回顾性分析。患者来自临床试验（NCT02716116）、德国的图表审查研究以及 LC-SCRUM-Japan、GENIE 和美国 COTA 数据库。在每个数据集计算了可以通过六种市售且广泛使用的 PCR 试剂盒检测到的具有 ex20ins 变体的患者比例。
总体而言，这项分析纳入了 636 例患有 EGFR ex20ins 突变的 NSCLC 患者，在所有数据源中鉴定出了 104 种独特的 EGFR ex20ins 变体。通过任何单独的 PCR 测试可以检测到的患者比例在各数据源中范围为 11.8%至 58.9%。
我们的发现表明，评估的 PCR 测试可能遗漏了超过 40%的患有 NSCLC 且携带有 EGFR ex20ins 突变的患者。基于 NGS 的遗传检测优于标准 PCR 检测，可以大大提高对 NSCLC 中 EGFR ex20ins 变体多样化谱的识别。
