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EGFR -TKIs一线治疗EGFR 复合突变非小细胞肺癌的疗效及耐药分析Efficacy and resistance of
EGFR -TKIs for first-line treatment for compoundEGFR mutations positive non-small cell lung cancer- 陆军军医大学学报 2022年44卷第24期 页码：2486-2492
- 作者机构：
1.510006 广州，华南理工大学医学院
2.510080 广州，广东省人民医院肿瘤医院肺内一科，广东省医学科学院
3.510080 广州，广东省心血管病研究所
- 作者简介：
[ 杨衿记，E-mail: yangjinji@gdph.org.cn YANG Jinji, E-mail: yangjinji@gdph.org.cn
- 基金信息：国家自然科学基金面上项目(81972164);广东省自然科学基金(2019A1515010931)
DOI：10.16016/j.2097-0927.202208119
中图分类号： R734.2;R969.4;R979.19收稿：2022-08-17，
修回：2022-09-21，
纸质出版：2022-12-30
- 稿件说明：
移动端阅览
管旭辉, 林晓程, 杨衿记.
EGFR -TKIs一线治疗EGFR 复合突变非小细胞肺癌的疗效及耐药分析[J]. 陆军军医大学学报, 2022,44(24):2486-2492.Xuhui GUAN, Xiaocheng LIN, Jinji YANG. Efficacy and resistance of
EGFR -TKIs for first-line treatment for compoundEGFR mutations positive non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2486-2492.管旭辉, 林晓程, 杨衿记.
EGFR -TKIs一线治疗EGFR 复合突变非小细胞肺癌的疗效及耐药分析[J]. 陆军军医大学学报, 2022,44(24):2486-2492. DOI： 10.16016/j.2097-0927.202208119.Xuhui GUAN, Xiaocheng LIN, Jinji YANG. Efficacy and resistance of
EGFR -TKIs for first-line treatment for compoundEGFR mutations positive non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2486-2492. DOI： 10.16016/j.2097-0927.202208119.
摘要
目的
2
观察
EGFR
复合同一外显子突变患者及其一线
EGFR
-TKIs耐药后基因突变谱特点，并探讨此类患者的临床治疗特征及其生存获益。
方法
2
纳入2010年1月至2019年4月于广东省肺癌研究所确诊的22例
EGFR
复合同一外显子突变非小细胞肺癌(non-small cell lung cancer
NSCLC)患者的生存获益情况，根据实体肿瘤(RECIST)1.1版进行靶向治疗疗效评价。并基于二代测序(next generation sequencing，NGS)技术对8例患者的基线基因突变情况及11例患者的一线应用
EGFR
-TKIs耐药后基因突变情况进行分析。
结果
2
22例患者中，21号外显子复合突变15例，18号外显子复合突变6例，19号外显子复合突变仅为1例。全组中位无进展生存期(median progression-free survival，mPFS)为9.9个月，其中21号外显子复合突变组的mPFS为9.5个月，18号外显子的mPFS为5.4个月，Kaplan-Meier生存曲线显示两组间PFS可能有差异趋势，但无统计学意义(
P
=0.27)。一线第一代
EGFR
-TKIs组与第二代
EGFR
-TKIs组的mPFS分别为13.8和9.7个月，无显著性差异(
P
=0.48)。NGS结果显示88%的
EGFR
复合突变基线存在
TP
53伴随突变，25%存在
NQO
1和
XRCC
1突变。一线
EGFR
-TKIs耐药后50%的患者出现T790M突变，25%出现
MET
扩增，耐药基因谱呈现较大的个体间差异。此外，19号外显子复合突变患者出现T790M获得性耐药突变后应用奥希替尼的疗效可能好于21号外显子复合突变。
结论
2
不同外显子之间，
EGFR
复合突变患者应用靶向治疗疗效可能有差异，但应用第一、二代
EGFR
-TKIs的疗效相似，且耐药基因特征与
EGFR
经典敏感单突变相类似。
Abstract
Objective
2
To observe the characteristics of mutation patterns in patients with compound
EGFR
mutations in the same exon and their resistance to
EGFR
TKIs
and to explore the clinical features and survival benefits among these non-small cell lung cancer (NSCLC) patients.
Methods
2
The survival benefits of 22 patients with compound
EGFR
mutations in the same exon were analyzed retrospectively Guangdong Lung Cancer Institute from January 2010 to April 2019
and the efficacy of targeted therapy was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST)
version 1.1. Next generation sequencing (NGS) technology was used to analyze the mutations of 8 patients at the baseline and 11 patients after the first-line
EGFR
TKIs.
Results
2
Among the enrolled 22 patients
there were 15 cases of compound mutation in exon 21
6 cases in exon 18
and only 1 case in exon 19. The median progression free survival (mPFS) was 9.9 months for the whole group
9.5 months for the patients with exon 21 compound mutation
and 5.4 months in those with exon 18. The Kaplan-Meier survival curve showed that there might be a trend of difference in PFS between the 2 groups
but there was no statistical significance (
P
=0.27). The mPFS of the first generation
EGFR
TKIs group and the second generation
EGFR
TKIs group were 13.8 and 9.7 months
respectively
with no significant difference (
P
=0.48). NGS results showed that 88% of compound
EGFR
mutations had
TP
53 concomitant mutations at baseline
and 25% had
NQO
1 and
XRCC
1 mutations. After first-line
EGFR
TKIs resistance
50% of the patients had T790M mutation and 25% had
MET
amplification. The expression profile of drug resistance genes showed individual differences. In addition
the efficacy of osimertinib for acquired T790M mutation in patients with compound mutation of exon 19 was better than that of exon 21.
Conclusion
2
Among different exons
the efficacy of targeted therapy in patients with compound
EGFR
mutations may be different
but the efficacy of the first and second generation
EGFR
TKIs is similar
and the profiles of drug resistance genes are similar to those of classic
EGFR
sensitive monomutations.
关键词
Keywords
references
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