Jain Amit, Lim Cindy, Gan Eugene MingJin, Ng David Zhihao, Ng Quan Sing, Ang Mei Kim, Takano Angela, Chan Kian Sing, Tan Wu Meng, Kanesvaran Ravindran, Toh Chee Keong, Loo Chian Min, Hsu Anne Ann Ling, Devanand Anantham, Lim Chong Hee, Koong Heng Nung, Koh Tina, Fong Kam Weng, Yap Swee Peng, Kim Su Woon, Chowbay Balram, Oon Lynette, Lim Kiat Hon, Lim Wan Teck, Tan Eng Huat, Tan Daniel Shao Weng
Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
Clinical Trials & Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore.
PLoS One. 2015 May 8;10(5):e0123587. doi: 10.1371/journal.pone.0123587. eCollection 2015.
This purpose of this study was to examine clinical-pathologic factors--particularly smoking and brain metastases--in EGFR mutation positive (M(+)) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI.
A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M(+) ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival.
444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M(+.) Amongst never-smokers (n=468), EGFR M(+) were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson's chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival.
The high prevalence of EGFR M(+) in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.
本研究旨在探讨临床病理因素——尤其是吸烟和脑转移——在表皮生长因子受体（EGFR）突变阳性（M(+)）肺腺癌（ADC）中的情况，以确定它们对接受一线EGFR酪氨酸激酶抑制剂（TKI）治疗患者生存的影响。
回顾性分析2009年1月至2013年4月在一家亚洲三级癌症中心确诊的所有ADC患者的EGFR突变检测经验。在该队列中，确定接受一线EGFR TKI治疗的晚期EGFR M(+) ADC患者，以确定影响无进展生存期和总生存期的因素。
742例接受EGFR突变检测的ADC患者中，444例（59.8%）为EGFR M(+)。在从不吸烟者（n = 468）中，女性EGFR M(+)占74.5%，男性占76.3%；在曾经吸烟者（n = 283）中，女性占53.3%，男性占35.6%。外显子20突变在重度吸烟者（>50包年和>20包年，Pearson卡方检验p分别为0.044和0.038）中更常见。211例接受姑息性一线TKI治疗的患者，中位无进展生存期和总生存期分别为9.2个月和19.6个月。26%的患者在诊断时已有脑转移。多因素分析显示，这对总生存期有显著不利影响（风险比1.85，可信区间1.09 - 3.16，p = 0.024）。没有证据表明吸烟状态对生存有显著影响。
在我们的患者群体中，EGFR M(+)的高患病率表明无论性别和吸烟状态如何，都有必要进行EGFR突变检测。吸烟状态和剂量对接受一线EGFR TKI治疗的患者的无进展生存期或总生存期没有影响。诊断时存在脑转移对总生存期有负面影响。
