免疫检查点抑制剂治疗携带表皮生长因子受体突变的非小细胞肺癌患者的临床结局。
Clinical outcomes of immune checkpoint inhibitors to treat non-small cell lung cancer patients harboring epidermal growth factor receptor mutations.
机构信息
Department of Clinical Trial, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China.
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
出版信息
BMC Pulm Med. 2023 May 5;23(1):158. doi: 10.1186/s12890-023-02466-9.
BACKGROUND
We aimed to determine the clinical. outcomes of various immune checkpoint inhibitor (ICI) combinations for the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The results predicted the treatment efficacy of these combinations.
METHODS
From July 15, 2016 to March 22, 2022, 85 NSCLC patients with EGFR mutations, enrolled at the Zhejiang Cancer Hospital, received ICI combinations after resistance to prior EGFR-tyrosine kinase inhibitors (EGFR-TKIs). These patients were diagnosed with EGFR mutations using an amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS). Survival times were analyzed using the Kaplan-Meier method and log-rank test.
RESULTS
Patients who received ICIs combined with anti-angiogenic therapy had longer progression-free survival (PFS) and overall survival (OS) than patients who received ICIs combined with chemotherapy. There was no significant difference in survival time between patients who received ICIs combined with chemotherapy and anti-angiogenic therapy and patients who received ICIs combined with anti-angiogenic therapy or ICIs combined with chemotherapy, which was due to the limitation sample size of patients who received ICIs combined with chemotherapy and anti-angiogenic therapy. Patients with L858R mutations had a longer PFS and OS than patients with exon 19 deletions. T790M negative patients benefited more from ICI combinations, compared with T790M positive patients. In addition, there was no significant difference in PFS and OS between patients with TP53 co-mutations and patients without a TP53 co-mutation. We also found that patients with prior first-generation EGFR-TKI resistance had longer PFS and OS than prior third-generation EGFR-TKI resistance patients. There was no new adverse event in this study.
CONCLUSIONS
EGFR-mutated patients who received ICIs combined with anti-angiogenic therapy had longer PFS and OS than patients with ICIs combined with chemotherapy. Patients with L858R or without T790M mutation benefited more from ICI combinations. Besides, patients with prior first-generation EGFR-TKI resistance could benefit more from ICIs combinations than prior third-generation EGFR-TKI resistance patients.
背景
我们旨在确定各种免疫检查点抑制剂（ICI）联合治疗表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的临床结局。结果预测了这些联合治疗的疗效。
方法
2016 年 7 月 15 日至 2022 年 3 月 22 日，85 例 EGFR 突变的 NSCLC 患者在浙江省肿瘤医院接受了先前 EGFR-酪氨酸激酶抑制剂（EGFR-TKIs）耐药后的 ICI 联合治疗。这些患者使用扩增阻滞突变系统 PCR（ARMS-PCR）和下一代测序（NGS）诊断为 EGFR 突变。使用 Kaplan-Meier 方法和对数秩检验分析生存时间。
结果
接受 ICI 联合抗血管生成治疗的患者无进展生存期（PFS）和总生存期（OS）长于接受 ICI 联合化疗的患者。接受 ICI 联合化疗和抗血管生成治疗的患者与接受 ICI 联合抗血管生成治疗或 ICI 联合化疗的患者的生存时间无显著差异，这是由于接受 ICI 联合化疗和抗血管生成治疗的患者样本量有限。L858R 突变患者的 PFS 和 OS 长于外显子 19 缺失患者。T790M 阴性患者从 ICI 联合治疗中获益更多，而 T790M 阳性患者则获益较少。此外，TP53 共突变患者与无 TP53 共突变患者的 PFS 和 OS 无显著差异。我们还发现，具有第一代 EGFR-TKI 耐药的患者的 PFS 和 OS 长于具有第三代 EGFR-TKI 耐药的患者。本研究未出现新的不良反应。
结论
接受 ICI 联合抗血管生成治疗的 EGFR 突变患者的 PFS 和 OS 长于接受 ICI 联合化疗的患者。L858R 或无 T790M 突变的患者从 ICI 联合治疗中获益更多。此外，具有第一代 EGFR-TKI 耐药的患者比具有第三代 EGFR-TKI 耐药的患者更能从 ICI 联合治疗中获益。
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