Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of University of Science and Technology (USTC), Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.
Front Immunol. 2023 May 17;14:1161718. doi: 10.3389/fimmu.2023.1161718. eCollection 2023.
INTRODUCTION: Platinum-based chemotherapy is still the standard of care for Epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) patients after developing EGFR-TKI resistance. However, no study focusing on the role of immuno checkpoint inhibitor (ICI) based treatments for EGFR mutated NSCLC patients who carried programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50% progressed after EGFR-TKI therapy. In this study, we retrospectively investigated the outcomes of ICI-based treatments for EGFR mutated NSCLC patients carried PD-L1 TPS≥50% after developing EGFR-TKI resistance and to explore the population that may benefited from ICI-based treatment. METHODS: We retrospectively collected data of advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation at Shanghai Chest Hospital between January 2018 and June 2021. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of this study. RESULTS: A total of 146 patients were included. Up to June 20th, 2022, median follow-up was 36.7 months (IQR, 12.5-44.2 months). Among the population, 66 patients (45.2%) received chemotherapy, the remaning (54.8%) received ICI-based treatment, including 56 patients(70.0%) received ICI combined with chemotherapy (IC) and 24 patients (30.0%) received ICI monotherapy (IM). In IC group,31 patients received ICI combined with chemotherapy,19 patients received ICI combined with antiangiogenic therapy and remaing received ICI combined with chemotherapy and antiangiogenic therapy. Survival analysis shown that patients who received ICI-based treatment had better progress-free survival (PFS) and overall survival (OS) compared with those treated with other therapy (median PFS, 10.0 vs. 4.0 months, P<0.001; median OS, 39.5 vs. 24.2 months, P<0.001). What's more, patients who treated with IC treatment had a superior survival time than those received IM treatment (median PFS, 10.3 vs. 7.0 months, P<0.001; median OS, 41.6 vs. 32.4 months, P<0.001). Subgroup analysis found that the PFS and OS benefit of IC was evident in all subgroups. CONCLUSIONS: For advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation, ICI-based treatment could provide a more favorable survival than classical chemotherapy. What' s more, compared with ICI monotherapy, ICI combined with chemotherapy seems to be the preferred treatment.
简介：表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）患者在出现 EGFR-TKI 耐药后，仍然以铂类为基础的化疗作为标准治疗。然而，目前尚无研究关注免疫检查点抑制剂（ICI）在 EGFR 突变 NSCLC 患者中的作用，这些患者在 EGFR-TKI 治疗后程序性死亡配体 1（PD-L1）肿瘤比例评分（TPS）大于 50%的情况下，进展后接受 ICI 治疗。在这项研究中，我们回顾性调查了 ICI 治疗 PD-L1 TPS 大于 50%的 EGFR 突变 NSCLC 患者在出现 EGFR-TKI 耐药后的治疗结果，并探讨了可能从 ICI 治疗中获益的人群。
方法：我们回顾性收集了 2018 年 1 月至 2021 年 6 月期间在上海胸科医院接受过 EGFR 突变且 PD-L1 TPS 大于 50%的、既往 EGFR-TKI 治疗失败且无 T790M 突变的晚期 NSCLC 患者的数据。无进展生存期（PFS）和总生存期（OS）用于评估本研究的结果。
结果：共纳入 146 例患者。截至 2022 年 6 月 20 日，中位随访时间为 36.7 个月（IQR，12.5-44.2 个月）。在人群中，66 例（45.2%）患者接受化疗，其余（54.8%）患者接受 ICI 治疗，包括 56 例（70.0%）患者接受 ICI 联合化疗（IC）和 24 例（30.0%）患者接受 ICI 单药治疗（IM）。在 IC 组中，31 例患者接受了 ICI 联合化疗，19 例患者接受了 ICI 联合抗血管生成治疗，其余患者接受了 ICI 联合化疗和抗血管生成治疗。生存分析显示，与接受其他治疗的患者相比，接受 ICI 治疗的患者具有更好的无进展生存期（PFS）和总生存期（OS）（中位 PFS，10.0 与 4.0 个月，P<0.001；中位 OS，39.5 与 24.2 个月，P<0.001）。更重要的是，接受 IC 治疗的患者的生存时间优于接受 IM 治疗的患者（中位 PFS，10.3 与 7.0 个月，P<0.001；中位 OS，41.6 与 32.4 个月，P<0.001）。亚组分析发现，IC 的 PFS 和 OS 获益在所有亚组中均明显。
结论：对于既往 EGFR-TKI 治疗失败且无 T790M 突变的 EGFR 突变和 PD-L1 TPS 大于 50%的晚期 NSCLC 患者，ICI 治疗比经典化疗能提供更有利的生存。此外，与 ICI 单药治疗相比，ICI 联合化疗似乎是首选治疗。
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