Efficacy and resistance of <italic style="font-style: italic">EGFR</italic>-TKIs for first-line treatment for compound <italic style="font-style: italic">EGFR</italic> mutations positive non-small cell lung cancer

Xuhui GUAN; Xiaocheng LIN; Jinji YANG

doi:10.16016/j.2097-0927.202208119

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Efficacy and resistance of EGFR-TKIs for first-line treatment for compound EGFR mutations positive non-small cell lung cancer

Monographic Reports: Targeted therapy of lung cancer | 更新时间：2026-02-13

- Efficacy and resistance of EGFR-TKIs for first-line treatment for compound EGFR mutations positive non-small cell lung cancer
- Journal of Army Medical University Vol. 44, Issue 24, Pages: 2486-2492(2022)
- 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：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81972164);the Natural Science Foundation of Guangdong Province(2019A1515010931)
- DOI：10.16016/j.2097-0927.202208119
  CLC： R734.2;R969.4;R979.19
- Received：17 August 2022，
  
  Revised：2022-09-21，
  
  Published：30 December 2022
- 稿件说明：
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Xuhui GUAN, Xiaocheng LIN, Jinji YANG. Efficacy and resistance of EGFR-TKIs for first-line treatment for compound EGFR mutations positive non-small cell lung cancer[J]. Journal of Army Medical University, 2022, 44(24): 2486-2492.
DOI：

Xuhui GUAN, Xiaocheng LIN, Jinji YANG. Efficacy and resistance of EGFR-TKIs for first-line treatment for compound EGFR 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

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

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

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(

=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(

=0.48)。NGS结果显示88%的

EGFR

复合突变基线存在

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

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

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

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

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 (

=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 (

=0.48). NGS results showed that 88% of compound

EGFR

mutations had

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

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

SUNG H, FERLAY J, SIEGEL R L, et al . Global cancer statistics 2020: GLOB OCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

HERBST R S, HEYMACH J V, LIPPMAN S M. Lung cancer[J]. N Engl J Med, 2008, 359(13): 1367-1380. DOI: 10.1056/nejmra0802714.

MOK T S, WU Y L, THONGPRASERT S, et al . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J ] . N Engl J Med, 2009, 361(10): 947-957. DOI: 10.1056/NEJMoa0810699.

ZHOU C C, WU Y L, CHEN G Y, et al . Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study[J ] . Lancet Oncol, 2011, 12(8): 735-742. DOI: 10.1016/S1470-2045(11)70184-X.

HAYASHI T, KOHSAKA S, TAKAMOCHI K, et al . Clinicopathological characteristics of lung adenocarcinoma with compound EGFR mutations[J ] . Hum Pathol, 2020, 103: 42-51. DOI: 10.1016/j.humpath.2020.07.007.

LI M, ZHOU C Z, YANG J J, et al . The in Cis compound EGFR mutations in Chinese advanced non- small cell lung cancer patients[J ] . Cancer Biol Ther, 2019, 20(8): 1097-1104. DOI: 10.1080/15384047.2019.1595280..

WEN Y S, CAI L, ZHANG X W, et al . Concurrent oncogene mutation profile in Chinese patients with stage Ib lung adenocarcinoma[J ] . Medicine, 2014, 93(29): e296. DOI: 10.1097/MD.0000000000000296.

YANG J C H, SEQUIST L V, GEATER S L, et al . Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6[J ] . Lancet Oncol, 2015, 16(7): 830-838. DOI: 10.1016/S1470-2045(15)00026-1.

MASOOD A, KANCHA R K, SUBRAMANIAN J. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: focus on afatinib[J]. Semin Oncol, 2019, 46(3): 271-283. DOI: 10.1053/j.seminoncol.2019.08.004.

SORIA J C, OHE Y, VANSTEENKISTE J, et al . Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J ] . N Engl J Med, 2018, 378(2): 113-125. DOI: 10.1056/NEJMoa1713137.

VOKES N I, CHAMBER S E, NGUYEN T, et al . Concurrent TP53 mutations facilitate resistance evolution in EGFR-mutant lung adenocarcinoma[J ] . J Thorac Oncol, 2022, 17(6): 779-792. DOI: 10.1016/j.jtho.2022.02.011.

TSENG J S, SU K Y, YANG T Y, et al . The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M[J ] . Oncotarget, 2016, 7(30): 48059-48069. DOI: 10.18632/oncotarget.10351.

CROSS D A E, ASHTON S E, GHIORGHIU S, et al . AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer[J ] . Cancer Discov, 2014, 4(9): 1046-1061. DOI: 10.1158/2159-8290.CD-14-0337.

WU S G, SHIH J Y. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer[J]. Mol Cancer, 2018, 17(1): 38. DOI: 10.1186/s12943-018-0777-1.

EIDE I J Z, HELLAND Å, EKMAN S, et al . Osimertinib in T790M-positive and-negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study)[J ] . Lung Cancer, 2020, 143: 27-35. DOI: 10.1016/j.lungcan.2020.03.009.

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⁰

Efficacy and resistance of EGFR-TKIs for first-line treatment for compound EGFR mutations positive non-small cell lung cancer

DOI：10.16016/j.2097-0927.202208119

摘要

Abstract

关键词

Keywords

references