Division of Hematology-Oncology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea.
Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea.
Anticancer Res. 2023 May;43(5):2343-2349. doi: 10.21873/anticanres.16399.
BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) improve long-term survival in advanced non-small cell lung cancer (NSCLC) and require robust predictive biomarkers for the selection of responders. This study investigated the optimal implementation of DNA damage repair (DDR) gene mutations to predict response to ICIs in real-world NSCLC patients.
We retrospectively reviewed 55 advanced NSCLC patients who had undergone targeted high-throughput sequencing and received ICIs. Patients with two or more DDR gene mutations were defined as DDR2 positive.
The patients' median age was 68 (range=44-82) years, and 48 (87.3%) were men. Seventeen patients (30.9%) showed ≥50% high programmed death-ligand 1 (PD-L1) expression. Ten patients (18.2%) received an ICI-chemotherapy combination as first-line therapy, and 38 (69.1%) received ICI monotherapy as more than second-line therapy. Fourteen patients (25.5%) were DDR2-positive. The objective response rate of patients with DDR2-positive or PD-L1 ≥50% was 45.5%, and that of patients with DDR2-negative and PD-L1 <50% was 11.1% (p=0.007). In the PD-L1 low expression subgroup (<50%), patients with DDR2-positive had improved progression-free survival (PFS) and overall survival (OS) after ICIs compared to those with DDR2-negative (PFS: 5.8 vs. 1.9 months, p=0.026, OS: 14.4 vs. 7.2 months, p=0.078). DDR2-positive patients or those with PD-L1 ≥50% (24, 43.6%) had statistically significant improvement in PFS and OS after ICIs compared to DDR2-negative and those with PD-L1 <50% (PFS: 4.4 vs. 1.9 months, p=0.006, OS: 11.6 vs. 7.2 months, p=0.037).
A dual biomarker combining DDR gene mutations and PD-L1 expression improves the prediction of response to ICIs in advanced NSCLC.
背景/目的：免疫检查点抑制剂 (ICI) 可改善晚期非小细胞肺癌 (NSCLC) 的长期生存，并需要强大的预测生物标志物来选择应答者。本研究旨在探讨 DNA 损伤修复 (DDR) 基因突变在预测真实世界 NSCLC 患者对 ICI 反应中的最佳应用。
我们回顾性分析了 55 例接受靶向高通量测序并接受 ICI 治疗的晚期 NSCLC 患者。存在两种或两种以上 DDR 基因突变的患者定义为 DDR2 阳性。
患者的中位年龄为 68 岁（范围=44-82 岁），48 例（87.3%）为男性。17 例（30.9%）患者 PD-L1 高表达≥50%。10 例（18.2%）患者一线治疗采用 ICI-化疗联合治疗，38 例（69.1%）患者二线以上采用 ICI 单药治疗。14 例（25.5%）患者为 DDR2 阳性。DDR2 阳性或 PD-L1≥50%患者的客观缓解率为 45.5%，而 DDR2 阴性且 PD-L1<50%的患者为 11.1%（p=0.007）。在 PD-L1 低表达亚组（<50%）中，与 DDR2 阴性相比，DDR2 阳性患者在接受 ICI 治疗后无进展生存期（PFS）和总生存期（OS）均有改善（PFS：5.8 个月 vs. 1.9 个月，p=0.026，OS：14.4 个月 vs. 7.2 个月，p=0.078）。与 DDR2 阴性且 PD-L1<50%的患者相比，DDR2 阳性或 PD-L1≥50%（24 例，43.6%）患者在接受 ICI 治疗后 PFS 和 OS 均有统计学显著改善（PFS：4.4 个月 vs. 1.9 个月，p=0.006，OS：11.6 个月 vs. 7.2 个月，p=0.037）。
联合 DDR 基因突变和 PD-L1 表达的双重生物标志物可提高晚期 NSCLC 患者对 ICI 反应的预测能力。
