Predictive value of clinical parameters in responses to epidermal growth factor-tyrosine kinase inhibitors as first-line therapy for stage Ⅳ non-small cell lung cancer

Linpeng ZHENG; Zihan XU; Guangkuo ZHU; Feng LI; Qiao YANG; Yongxin YU; Jianguo SUN

doi:10.16016/j.1000-5404.201809143

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Predictive value of clinical parameters in responses to epidermal growth factor-tyrosine kinase inhibitors as first-line therapy for stage Ⅳ non-small cell lung cancer

Clinical Medicine | 更新时间：2026-01-09

- Predictive value of clinical parameters in responses to epidermal growth factor-tyrosine kinase inhibitors as first-line therapy for stage Ⅳ non-small cell lung cancer
- Journal of Third Military Medical University Vol. 41, Issue 4, Pages: 346-352(2019)
- 作者机构：
  
  400037 重庆，陆军军医大学(第三军医大学)第二附属医院全军肿瘤研究所
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81672841);the Clinical Science Research from Xinqiao Hospital of Army Medical University(2014YLC08)
- DOI：10.16016/j.1000-5404.201809143
  CLC： R734.2;R969.4;R979.1
- Received：20 September 2018，
  
  Revised：2018-11-01，
  
  Published：28 February 2019
- 稿件说明：
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Linpeng ZHENG, Zihan XU, Guangkuo ZHU, et al. Predictive value of clinical parameters in responses to epidermal growth factor-tyrosine kinase inhibitors as first-line therapy for stage Ⅳ non-small cell lung cancer[J]. Journal of Third Military Medical University, 2019, 41(4): 346-352.
DOI：

Linpeng ZHENG, Zihan XU, Guangkuo ZHU, et al. Predictive value of clinical parameters in responses to epidermal growth factor-tyrosine kinase inhibitors as first-line therapy for stage Ⅳ non-small cell lung cancer[J]. Journal of Third Military Medical University, 2019, 41(4): 346-352. DOI： 10.16016/j.1000-5404.201809143.

摘要

目的

通过分析临床参数与表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factorreceptor-tyrosine kinase inhibitors

EGFR-TKIs)疗效的关系，为一线Ⅳ期非小细胞肺癌(non-small cell lung cancer，NSCLC)EGFR-TKIs治疗疗效寻找简易的标志物。

方法

回顾性分析2010-2016年在本院接受一线EGFR-TKIs (厄洛替尼、吉非替尼、埃克替尼)治疗的Ⅳ期EGFR阳性突变NSCLC患者的临床参数与疗效的关系。

结果

共纳入123例，其中男性43例，女性80例，年龄28~84岁，客观缓解率(objective response rate，ORR)47.97%，疾病控制率(disease control rate，DCR)100%，中位无进展生存期(median progression-free survival，mPFS)11.0个月，中位总生存期(median overall survival，mOS) 22.7个月。单因素分析显示治疗前低NSE、CA125或Cyfra21-1者PFS较长(14.2

9.1个月，

0.001；12.4

9.5个月，

=0.024；12.3

9.5个月，

=0.033)。而PS评分0~1分，低NSE、CA125、Cyfra21-1或CA15-3者OS较长(mOS：24.0

16.5个月，

=0.001；27.7

17.3个月，

0.001；25.4

20.2个月，

=0.002；25.7

18.1个月，

=0.027；25.5

18.7个月，

=0.009)。多因素分析结果显示CA125和NSE是PFS的独立影响因素，而CA125、NSE、CA15-3、肝转移、PS评分是OS的独立影响因素。CA125、Cyfra21-1、CA15-3和NSE 4个参数中多个参数升高的PFS、OS较单个参数升高短(mPFS：9.3

11.8个月，

=0.045；mOS：18.7

27.4个月，

=0.001)。

结论

治疗前低水平的CA125或NSE预示着Ⅳ期NSCLC一线EGFR-TKIs治疗的PFS较长，而PS评分0~1分

低水平的NSE、CA125或CA15-3则预示OS较长。CA125、Cyfra21-1、CA15-3和NSE 4个临床参数联合有望成为预测Ⅳ期NSCLC一线EGFR-TKIs疗效的简易标志物。

Abstract

Objective

To analyze the relationship between the clinical parameters and the efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors (EGFR-TKIs) as the first-line therapy in patients with stage Ⅳ non-small cell lung cancer (NSCLC) and identify the clinical markers for predicting the patients' responses to the treatment.

Methods

The clinical data were retrospectively reviewed for the patients with stage Ⅳ EGFR mutation-positive NSCLC receiving EGFR-TKIs (erlotinib

gefitinib

and icotinib) as the first-line therapy in our hospital between January

2010 and December

2016

and the relationship between the patients' clinical parameters and responses to the treatment were analyzed.

Results

A total of 123 patients (43 males and 80 females

aged ranging from 28 to 84 years) were included in this study. The objective response rate (ORR) of the overall patients was 47.97%

the disease control rate (DCR) was 100%

the median progression-free survival (mPFS) time was 11.0 months

and the median overall survival (OS) time was 22.7 months. Univariate analysis showed that the patients with low levels of neuronspecific enolase (NSE)

carbohydrate antigen 125 (CA125) or Cyfra21-1 before the treatment had significantly prolonged mPFS time (NES: 14.2

9.1 months

0.001; CA125: 12.4

9.5 months

=0.024; Cyfra21-1: 12.3

9.5 months

=0.033); the mOS time was significantly prolonged in patients with ECOG performance status of 0~1 (24.0

16.5 months

=0.001) and low levels of NSE (27.7

17.3 months

0.001)

CA125 (25.4

20.2 months

=0.002)

Cyfra21-1 (25.7

18.1 months

=0.027) or CA15-3 (25.5

18.7 months

=0.009). Multivariate analysis suggested that CA125 and NSE were independent prognostic factors of PFS

and CA125

NSE

CA15-3

hepatic metastasis and performance status were independent prognostic factors of the OS time. Combined analysis of CA125

Cyfra21-1

CA15-3 and NSE showed that compared with those with elevation of a single factor

the patients with elevation of multiple factors had shorter mPFS time (9.3

11.8 months

=0.045) and also shorter mOS time (18.7

27.4 months

=0.001).

Conclusion

Low levels of CA125 or NSE before first-line EGFR-TKIs treatment are associated with longer PFS time of the patients with stage Ⅳ NSCLC

while performance status of 0~1 and low levels of NSE

CA125 or CA15-3 are associated with a longer OS time of the patients. The combination of CA125

Cyfra21-1

CA15-3 and NSE is expected to serve as a simple indicator for predicting the efficacy of firstreceptor-line EGFR-TKIs therapy in patients with stage Ⅳ NSCLC.

关键词

Keywords

references

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