EGFR突变丰度预测EGFR TKI治疗非小细胞肺癌的疗效

javacoder

来自广东省人民医院肿瘤中心的研究人员发表了题为“Relative Abundance of EGFR Mutations Predicts Benefit From Gefitinib Treatment for Advanced Non–Small-Cell Lung Cancer”的文章，发现EGFR突变丰度能预测EGFR TKI治疗非小细胞肺癌的疗效，这将改变肺癌治疗策略。这一研究成果公布在世界顶级肿瘤学杂志《Journal of clinical oncology》上。

文章的通讯作者是广东省人民医院肿瘤中心吴一龙教授，吴一龙教授曾在国内首先提出肿瘤单病种首席专家制，建立了第一个真正意义的肺癌多学科综合治疗科。在肿瘤领域率先引进循证医学，是该领域的学术带头人。主编专著《肺癌多学科综合治疗的理论与实践》、《现代肺癌病理与临床》等。

据南方日报报道，此前医学界一般认为，符合女性、不吸烟、腺癌这3个因素的肺癌病人，使用易瑞沙或特罗凯这两种分子靶向药物，治疗有效率可达60%。几年来，经过吴一龙等中外专家的科研证明，其实基因突变才是关键因素，如果检测出有EGFR(表皮生长因子受体)突变的肺癌病人，服用这两种分子靶向药物，治疗有效率可达70%到80%，很多晚期病人已经存活3—5年，最长7年。



但为什么还有20%到30%的肺癌病人明明查出有基因突变，却服药无效或者短时间后就失效？这篇论文揭开了这个难题的谜底：原来，疗效不仅与是否有基因突变相关，还与基因突变的量有密切关系。


研究人员利用两种敏感度不同的检测方法，一种是只能查出30%以上的EGFR突变量，另一种是连一个细胞发生突变也能查出，分别筛查出两组肺癌病人，都给予靶向药物治疗。结果发现，第一组即基因突变量大的肺癌病人，疗效特别好，而第二组即突变量小的病人疗效则很一般，差别非常明显。



这个研究将改变肺癌治疗策略。目前，对肺癌病人，一般先查有没有EGFR突变，如果有突变，就建议吃靶向药物。今后要对有突变的病人进一步分类，根据突变量的大小，决定是否吃靶向药物，制定个性化治疗方案。





原文出处：

Relative Abundance of EGFR Mutations Predicts Benefit From Gefitinib Treatment for Advanced Non–Small-Cell Lung Cancer

Abstract
Purpose Our aim was to determine whether abundance of epidermal growth factor receptor (EGFR) mutations in tumors predicts benefit from treatment with EGFR–tyrosine kinase inhibitors (TKIs) for advanced non–small-cell lung cancer (NSCLC).

Patients and Methods We detected EGFR mutations in 100 lung cancer samples using direct DNA sequencing and amplification refractory mutation system (ARMS). Mutation-positive tumors by both methods carried high abundance of EGFR mutations. Tumors that were mutation positive by ARMS but mutation negative by direct DNA sequencing harbored low abundance of EGFR mutations. Mutation-negative tumors by both methods carried wild-type EGFR. All patients received gefitinib treatment. The correlation between EGFR mutation abundance and clinical benefit from gefitinib treatment was analyzed.

Results Of 100 samples, 51 and 18 harbored high and low abundances of EGFR mutations, respectively; 31 carried wild-type EGFR. Median progression-free survival (PFS) was 11.3 (95% CI, 7.4 to 15.2) and 6.9 months (95% CI, 5.5 to 8.4) in patients with high and low abundances of EGFR mutations, respectively (P = .014). Median PFS of patients with low abundance of EGFR mutations was significantly longer than that of those with wild-type tumors (2.1 months; 95% CI, 1.0 to 3.2; P = .010). Objective response rates (ORRs) were 62.7%, 44.4%, and 16.1%, and overall survival (OS) rates were 15.9 (95% CI, 13.4 to 18.3), 10.9 (95% CI, 2.7 to 19.1), and 8.7 months (95% CI, 4.6 to 12.7) for patients with high abundance of EGFR mutations, low abundance of EGFR mutations, and wild-type EGFR, respectively. The difference between patients with high and low abundances of EGFR mutations was not significant regarding ORR and OS.

Conclusion The relative EGFR mutation abundance could predict benefit from EGFR-TKI treatment for advanced NSCLC.

javacoder

问题是现在能检测所谓的突变的风度吗？

升升不息

其实就是它的高低表达，这个是可以测出来的

javacoder

奥 明白了 谢谢

祥云

没有基因突变吃易瑞莎行吗

javacoder

@祥云，也有有效的可能 如果没有更好的办法可以试着吃一段看看效果