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免疫治疗联合方案优于单药治疗用于 EGFR 突变型非小细胞肺癌对 EGFR-TKIs 的获得性耐药。

Superior efficacy of immunotherapy-based combinations over monotherapy for EGFR-mutant non-small cell lung cancer acquired resistance to EGFR-TKIs.

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Medical Oncology, Cancer Hospital of Huanxing Chaoyang District Beijing, Beijing, China.

出版信息

Thorac Cancer. 2020 Dec;11(12):3501-3509. doi: 10.1111/1759-7714.13689. Epub 2020 Oct 19.

Abstract

BACKGROUND

While prospective clinical studies on immunotherapy in epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) are ongoing, this study aimed to investigate the outcomes of immunotherapy combinations in such a population in a real-world setting.

METHODS

The clinical data of pretreated EGFR-mutated NSCLC patients who acquired EGFR-TKI resistance and received immunotherapy were retrospectively analyzed in this study. Progression-free survival (PFS) was assessed using the Kaplan-Meier log-rank test, and univariate and multivariate analysis were performed.

RESULTS

A total of 31 patients were analyzed in this study. A total of 25 (80.6%) patients received combination immunotherapy. In the univariate analysis, patients who received combination immunotherapy seemingly acquired longer PFS than those who received monotherapy, although there was no significant difference (3.42 months vs. 1.61; P = 0.078; hazard ratio (HR) 0.43, 95% CI: 0.16-1.13). Patients who received antiangiogenic drugs prior to immunotherapy acquired better PFS (3.42 months vs. 1.58; P = 0.027; HR 0.37, 95% CI: 0.15-0.93), while patients with liver metastasis had inferior PFS (2.04 months vs. 3.42; P = 0.031; HR 2.83, 95% CI: 1.05-7.60). Furthermore, multivariate analysis confirmed that the above three factors had independent prognostic value.

CONCLUSIONS

The study revealed that immunotherapy combinations are better choices than single-agent regimens in previously treated and EGFR-mutant NSCLC patients with progressive disease. In addition, antiangiogenic drugs administered before immunotherapy might be a favorable prognostic factor, while liver metastasis was associated with a short PFS in this setting. In future, more robust and prospective clinical trial results are expected to guide clinical practice.

KEY POINTS

Significant study findings Immunotherapy-based combination therapies are better choices than single-agent regimens in heavily treated EGFR-mutant NSCLC patients. What this study adds Patients without liver metastasis and with prior antiangiogenic drugs obtained more benefit from immunotherapy in this setting.

摘要

背景

虽然针对表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者在获得 EGFR 酪氨酸激酶抑制剂(TKI)耐药后的免疫治疗的前瞻性临床研究正在进行中,但本研究旨在真实世界环境中研究此类人群中免疫治疗联合的结果。

方法

本研究回顾性分析了既往接受 EGFR 突变 NSCLC 治疗且发生 EGFR-TKI 耐药后接受免疫治疗的患者的临床数据。使用 Kaplan-Meier 对数秩检验评估无进展生存期(PFS),并进行单因素和多因素分析。

结果

本研究共分析了 31 例患者。共有 25 例(80.6%)患者接受了联合免疫治疗。在单因素分析中,尽管联合免疫治疗组的患者似乎比单药治疗组获得更长的 PFS,但差异无统计学意义(3.42 个月比 1.61 个月;P = 0.078;风险比(HR)0.43,95%CI:0.16-1.13)。在接受免疫治疗之前接受抗血管生成药物治疗的患者具有更好的 PFS(3.42 个月比 1.58 个月;P = 0.027;HR 0.37,95%CI:0.15-0.93),而存在肝转移的患者 PFS 较差(2.04 个月比 3.42 个月;P = 0.031;HR 2.83,95%CI:1.05-7.60)。此外,多因素分析证实了上述三个因素具有独立的预后价值。

结论

该研究表明,在先前接受过治疗且 EGFR 突变的 NSCLC 患者中,与单药治疗相比,免疫治疗联合治疗是更好的选择。此外,免疫治疗前使用抗血管生成药物可能是一个有利的预后因素,而在此情况下肝转移与较短的 PFS 相关。在未来,预计将有更多稳健的前瞻性临床试验结果来指导临床实践。

关键点

  • 重要的研究发现

  • 在经过大量治疗的 EGFR 突变 NSCLC 患者中,基于免疫治疗的联合治疗方案优于单药治疗方案。

  • 本研究新增内容

  • 在此情况下,无肝转移且有既往抗血管生成药物治疗的患者从免疫治疗中获益更多。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df9/7705617/e256dea4de9a/TCA-11-3501-g001.jpg

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