免疫检查点抑制剂联合安罗替尼治疗 EGFR-TKI 耐药的 EGFR 突变型 NSCLC 患者的后线疗效和安全性：一项单中心回顾性研究。

The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study.

机构信息

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

出版信息

Cancer Immunol Immunother. 2024 May 17;73(7):134. doi: 10.1007/s00262-024-03712-7.

BACKGROUND

Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy.

METHODS

A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR).

RESULTS

The median follow-up period was 28.6 months (range: 2.3-54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2-7.4 months), and the median OS was 17.1 months (95% CI 12.0-22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1-2, and no increase in adverse events was observed compared to monotherapy.

CONCLUSION

Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.

背景

EGFR-TKI 耐药后的有效治疗是临床关注的焦点。我们旨在研究安罗替尼联合抗 PD-1/PD-L1 抗体在 EGFR 突变 NSCLC 患者 TKI 治疗失败后的二线治疗中的疗效和安全性，并探讨治疗疗效的独立预测因素。

方法

本研究回顾性纳入 71 例经证实的晚期 EGFR 突变 NSCLC 患者，这些患者在接受标准 EGFR-TKI 治疗后进展，并且在接受多线治疗后仍未缓解。大多数患者之前至少接受过三线治疗。所有患者均接受安罗替尼联合抗 PD-1 或抗 PD-L1 治疗。通过不良事件发生率评估联合治疗的安全性。通过生存分析（OS、PFS、ORR、DCR）评估方案的疗效。

结果

中位随访时间为 28.6 个月（范围：2.3-54.0 个月），中位治疗线数为 4 线。总体缓解率（ORR）和疾病控制率（DCR）分别为 19.7%和 77.5%。中位 PFS 为 5.8 个月（95%CI 4.2-7.4 个月），中位 OS 为 17.1 个月（95%CI 12.0-22.3 个月）。接受免疫检查点抑制剂联合安罗替尼治疗的患者颅内客观缓解率（ORR）为 38.5%，疾病控制率（DCR）为 80.8%。基线时 ECOG 表现状态<2 是 PFS 的独立保护因素。转移器官和 ECOG 表现状态是预测 OS 的独立参数。66 例（93.0%）患者出现治疗相关不良事件；大多数不良事件为 1-2 级，与单药治疗相比，不良事件无增加。