Foundation Medicine Inc., Cambridge, Massachusetts.
Cone Health, Cancer Center at Wesley Long, Greensboro, North Carolina.
Clin Cancer Res. 2016 Jul 1;22(13):3281-5. doi: 10.1158/1078-0432.CCR-15-1668. Epub 2016 Mar 1.
Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation.
A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed.
Pathology reports were available for 250 consecutive cases with classical EGFR Δex19 (amino acids 743-754) and were reviewed to assess previous non-hybrid capture-based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR Δex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed.
CGP identifies drug-sensitive EGFR Δex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281-5. ©2016 AACR.
可靠检测出具有药物敏感性的激活型 EGFR 突变，对于晚期非小细胞肺癌（NSCLC）的治疗至关重要，但此类检测通常采用多种平台进行，其中许多平台缺乏严格的分析验证。
为了在临床治疗过程中做出治疗决策，根据个别治疗医生的要求，对大量 NSCLC 病例进行了经过充分验证的、基于杂交捕获的全面基因组分析（CGP）检测。在这些病例中，有 400 例 EGFR 外显子 19 缺失（Δex19）的患者，对其进行了分析，并对可用的临床病史进行了回顾。
有 250 例连续的 EGFR 外显子 19 缺失（经典 EGFR Δex19，氨基酸 743-754）病例提供了病理报告，对其进行了回顾，以评估之前基于非杂交捕获的 EGFR 检测。在有 EGFR 检测结果的 71 例病例中，有 12 例（17%）先前检测为阴性，其中 46 例中有 8 例（17%）为同一活检进行了分析。独立地，6 例 C-螺旋 EGFR Δex19 中有 5 例（83%）先前检测为阴性。在这些患者中有一部分可获得临床结局信息，观察到他们对 EGFR 抑制剂治疗有明显获益。
CGP 可在经过 EGFR 检测且结果为阴性的 NSCLC 病例中检测到具有药物敏感性的 EGFR Δex19。鉴于在携带这些改变的患者中，EGFR 酪氨酸激酶抑制剂在无进展生存期方面的获益已得到证实，因此在晚期 NSCLC 的初始表现和 EGFR 突变或其他驱动改变的检测结果为阴性时，应考虑 CGP。临床癌症研究；22(13)；3281-5. 2016 AACR.
