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非小细胞肺癌患者在病情逐渐进展后持续使用表皮生长因子受体酪氨酸激酶抑制剂治疗,联合或不联合化疗。

Continuous EGFR tyrosine kinase inhibitor treatment with or without chemotherapy beyond gradual progression in non-small cell lung cancer patients.

作者信息

Peng Ling, Wang Yina, Tang Yemin, Zeng Lei, Liu Junfang, Zeng Zhu, Liu Jian, Shi Peng, Ye Xianghua, Zhao Qiong

机构信息

Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou.

Department of Medical Statistics, Children's Hospital of Fudan University.

出版信息

Onco Targets Ther. 2017 Aug 28;10:4261-4267. doi: 10.2147/OTT.S143569. eCollection 2017.

Abstract

BACKGROUND

Several clinical studies have demonstrated that continuous administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could provide additional survival benefit for advanced non-small cell lung cancer (NSCLC) patients who had benefited from prior EGFR TKI therapy. However, whether EGFR TKI combined with chemotherapy could further prolong survival in patients with gradual progression is still unclear. The present study was conducted to evaluate the clinical outcome of continuous EGFR TKI treatment in combination with chemotherapy (combination group) versus continuous EGFR TKI treatment only (monotherapy group) in such a clinical setting.

METHODS

We designed a cohort study to collect all chart data of NSCLC patients treated with EGFR TKI in our institution from February 2012 to December 2015 retrospectively and followed up the clinical outcome of EGFR TKI monotherapy or therapy in combination with chemotherapy until April 2017 prospectively. All eligible patients had to meet the criteria of gradual progression. The time interval of progression-free survival 1 (PFS1, gradual progression or death) to PFS2 (off-EGFR TKI progression), and overall survival (OS) between the above 2 groups were used in survival analysis.

RESULTS

In all, 50 patients were included in our study. Patients' baseline characteristics were well balanced. Exon 19 deletion mutations and L858R point mutations were detected in 16 and 8 patients, respectively. Twenty, 22, and 8 patients were treated with EGFR TKI in the first, second, and third line setting, respectively. The time interval from PFS1 to PFS2 was 92 and 37 days (monotherapy vs combination), respectively (hazard ratio [HR] =1.16, 95% confidence interval [CI]: 0.61-2.21, =0.652). The median OS in the monotherapy group and combination group was 696 and 799 days, respectively (HR =0.74, 95% CI: 0.33-1.71, =0.501). There were no statistical differences between the 2 groups in terms of the time interval from PFS1 to PFS2 and OS.

CONCLUSION

Our results suggested that compared with EGFR TKI monotherapy, its combination with chemotherapy beyond gradual progression may not confer a significant survival benefit to NSCLC patients. Further prospective studies are warranted to reinforce the results of the study.

摘要

背景

多项临床研究表明,持续给予表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)可为先前从EGFR TKI治疗中获益的晚期非小细胞肺癌(NSCLC)患者带来额外的生存益处。然而,EGFR TKI联合化疗是否能进一步延长病情逐渐进展患者的生存期仍不清楚。本研究旨在评估在这种临床情况下,持续EGFR TKI联合化疗(联合治疗组)与单纯持续EGFR TKI治疗(单药治疗组)的临床疗效。

方法

我们设计了一项队列研究,回顾性收集2012年2月至2015年12月在我院接受EGFR TKI治疗的NSCLC患者的所有病历资料,并前瞻性随访EGFR TKI单药治疗或联合化疗的临床疗效至2017年4月。所有符合条件的患者必须满足病情逐渐进展的标准。生存分析采用无进展生存期1(PFS1,病情逐渐进展或死亡)至无进展生存期2(停用EGFR TKI后病情进展)的时间间隔以及上述两组之间的总生存期(OS)。

结果

本研究共纳入50例患者。患者的基线特征均衡。分别在16例和8例患者中检测到外显子19缺失突变和L858R点突变。分别有20例、22例和8例患者在一线、二线和三线治疗中接受EGFR TKI治疗。从PFS1到PFS2的时间间隔分别为92天和37天(单药治疗组与联合治疗组)(风险比[HR]=1.16,95%置信区间[CI]:0.61-2.21,P=0.652)。单药治疗组和联合治疗组的中位OS分别为696天和799天(HR=0.74,95%CI:0.33-1.71,P=0.501)。两组在从PFS1到PFS2的时间间隔和OS方面无统计学差异。

结论

我们的结果表明,与EGFR TKI单药治疗相比,其联合化疗用于病情逐渐进展后的NSCLC患者可能不会带来显著的生存益处。需要进一步的前瞻性研究来强化本研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5757/5584902/e8481b27f791/ott-10-4261Fig1.jpg

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