Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
J Thorac Oncol. 2017 Mar;12(3):585-590. doi: 10.1016/j.jtho.2016.09.001. Epub 2016 Sep 14.
The evolution of EGFR tyrosine kinase inhibitors (TKIs) has changed the landscape of disease for a subset of patients with NSCLC. Most patients with an EGFR mutation respond to these drugs; however, a proportion show limited or no tumor response. We explored the impact of co-mutation (double or multiple mutation), compared with a single mutation, of the EGFR gene on response to TKIs in a series of patients with metastatic NSCLC.
We retrospectively analyzed the mutation profiles of nonsquamous NSCLC tested at Royal Prince Alfred Hospital between 2012 and 2015 by MassArray using the OncoCarta v1.0 panel. Patients with metastatic disease whose tumors had sensitizing EGFR mutation(s) were included. The primary end point was progression-free survival (PFS). We used the Kaplan-Meier method for PFS and overall survival; the log rank test was used to compare groups with and without co-mutation. Multivariable analysis was done for PFS; response rate was assessed using chi-square and logistic regression analysis.
A total of 62 patients were included, and of these, eight (12.9%) had a co-mutation. The median PFS and overall survival times were 11.5 and 26.3 months, respectively. Patients with EGFR co-mutation had a significantly shorter median PFS than those with a single mutation (5.7 months versus 12.3 months, p = 0.02). The response rate to TKIs was significantly worse in those with co-mutation compared with in those without co-mutation (38% versus 89%, p < 0.001).
Taking into account the small number of patients in this study, PFS in patients with EGFR co-mutation appeared significantly shorter, and response rate significantly lower, than in patients with a single mutation. Data from multipanel testing may identify subgroups of patients who are likely to respond poorly to standard treatment. Clarification of these subgroups may improve patient care.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）的发展改变了一部分非小细胞肺癌（NSCLC）患者的疾病格局。大多数 EGFR 突变的患者对这些药物有反应；然而，一部分患者表现出有限的或没有肿瘤反应。我们探讨了 EGFR 基因的共突变（双突变或多突变）与单一突变相比，对一系列转移性 NSCLC 患者对 TKI 反应的影响。
我们通过 MassArray 使用 OncoCarta v1.0 面板，对 2012 年至 2015 年在皇家阿尔弗雷德王子医院进行的非鳞状 NSCLC 进行了回顾性分析。纳入了患有转移性疾病且肿瘤具有敏感 EGFR 突变的患者。主要终点是无进展生存期（PFS）。我们使用 Kaplan-Meier 方法进行 PFS 和总生存期分析；使用对数秩检验比较有和无共突变的组。对 PFS 进行多变量分析；使用卡方检验和逻辑回归分析评估反应率。
共纳入 62 例患者，其中 8 例（12.9%）存在共突变。中位 PFS 和总生存期分别为 11.5 个月和 26.3 个月。EGFR 共突变患者的中位 PFS 明显短于单一突变患者（5.7 个月比 12.3 个月，p=0.02）。共突变患者的 TKI 反应率明显低于无共突变患者（38%比 89%，p<0.001）。
考虑到本研究患者数量较少，EGFR 共突变患者的 PFS 明显较短，反应率明显较低。多面板检测数据可能确定对标准治疗反应不佳的患者亚组。明确这些亚组可能改善患者的治疗效果。
