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EGFR 突变型 NSCLC 患者接受 EGFR TKI 治疗的临床结局有何预测因素?

Is there any predictor for clinical outcome in EGFR mutant NSCLC patients treated with EGFR TKIs?

机构信息

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.

出版信息

Cancer Chemother Pharmacol. 2014 May;73(5):1063-70. doi: 10.1007/s00280-014-2442-8. Epub 2014 Mar 25.

Abstract

BACKGROUND

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have demonstrated some dramatic response rate and prolonged progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, PFS and overall survival (OS) among those patients who were treated with EGFR TKIs are inconsistent and unpredictable. In this study, we evaluated predictors of clinical outcome in EGFR mutant NSCLC patients treated with EGFR TKIs.

METHODS

A total of 148 patients who had metastatic or recurrent NSCLC with activating EGFR mutation treated with either erlotinib or gefitinib as a first-line (n = 10) and a second-line or more treatment (n = 138) were retrospectively reviewed.

RESULTS

The median follow-up duration was 21.9 months (range, 1.1-62.5). The median PFS and OS for a total 148 patients were 10.6 months (95 % CI 9.0-12.2) and 21.8 months (95 % CI 18.5-25.1), respectively. The survival outcomes were similar between the first-line and second-line or more line of treatment of EGFR TKIs (P = 0.512 for PFS, P = 0.699 for OS). Although a high number of metastasis sites (3-6 vs. 1-2) were associated with shorter PFS and OS (median PFS 9.9 vs. 11.9 months, P = 0.019; median OS 16.4 vs. 22.2 months, P = 0.021, respectively) in univariate analysis, but not in multivariate analysis. According to the clinical and molecular markers by multivariate analysis, there were no significant differences in PFS. When PFS was dichotomized by median 11 months for 105 patients treated with EGFR TKIs as second-line therapy, no significant differences in any clinical or molecular features were found between longer PFS and shorter PFS groups.

CONCLUSIONS

Despite the inconsistencies in PFS among EGFR mutant patients treated with EGFR TKIs, no significant differences of clinical features were noted, thereby suggesting a need for more understanding of the heterogeneity of underlying biology.

摘要

背景

表皮生长因子受体 (EGFR) 的酪氨酸激酶抑制剂 (TKI) 在具有激活 EGFR 突变的晚期非小细胞肺癌 (NSCLC) 患者中显示出了一些显著的反应率和延长的无进展生存期 (PFS)。然而,接受 EGFR TKI 治疗的患者的 PFS 和总生存期 (OS) 并不一致且不可预测。在这项研究中,我们评估了接受 EGFR TKI 治疗的 EGFR 突变型 NSCLC 患者临床结局的预测因素。

方法

回顾性分析了 148 例接受厄洛替尼或吉非替尼一线(n = 10)和二线或以上治疗(n = 138)治疗的转移性或复发性具有激活 EGFR 突变的 NSCLC 患者。

结果

中位随访时间为 21.9 个月(范围,1.1-62.5)。148 例患者的中位 PFS 和 OS 分别为 10.6 个月(95%CI 9.0-12.2)和 21.8 个月(95%CI 18.5-25.1)。EGFR TKI 一线和二线或以上治疗的生存结果相似(PFS 的 P = 0.512,OS 的 P = 0.699)。尽管转移部位较多(3-6 个 vs. 1-2 个)与较短的 PFS 和 OS 相关(中位 PFS 9.9 个月 vs. 11.9 个月,P = 0.019;中位 OS 16.4 个月 vs. 22.2 个月,P = 0.021),但在多变量分析中则不然。根据多变量分析的临床和分子标志物,在 PFS 方面没有显著差异。当将 105 例接受 EGFR TKI 二线治疗的患者的 PFS 中位数为 11 个月进行二分法时,在较长 PFS 和较短 PFS 组之间,任何临床或分子特征均无显著差异。

结论

尽管接受 EGFR TKI 治疗的 EGFR 突变患者的 PFS 不一致,但并未发现临床特征有显著差异,这表明需要进一步了解潜在生物学的异质性。

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