Center for Lung Cancer, Division of Hematology and Oncology, Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Research Institute, National Cancer Center, Goyang, Korea.
Cancer Res Treat. 2024 Jan;56(1):70-80. doi: 10.4143/crt.2023.482. Epub 2023 Jun 21.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC.
This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling.
A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS.
NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）显著改善了 EGFR 突变（EGFRm）非小细胞肺癌（NSCLC）患者的生存；然而，它们对肿瘤微环境（TME）的影响尚不清楚。我们评估了新辅助厄洛替尼治疗（NE）对可手术 EGFRm NSCLC 患者 TME 的影响。
这是一项单臂 II 期临床试验，用于 EGFRm NSCLC （EGFR 外显子 19 缺失或 L858R 突变）的新辅助/辅助厄洛替尼治疗。患者接受 2 个周期的 NE（每天 150mg）治疗 4 周，然后根据观察到的 NE 反应进行手术和辅助厄洛替尼或长春瑞滨加顺铂治疗。根据基因表达分析和突变分析评估 TME 变化。
共纳入 26 例患者；中位年龄为 61 岁，69%为女性，88%为 IIIA 期，62%为 L858R 突变。在接受 NE 的 25 例患者中，客观缓解率为 72%（95%可信区间，52.4%至 85.7%）。无疾病进展和总生存（OS）的中位时间分别为 17.9 个月（95%可信区间，10.5 至 25.4）和 84.7 个月（95%可信区间，49.7 至 119.8）。切除组织中的基因集富集分析显示白细胞介素、补体、细胞因子、转化生长因子β和 hedgehog 通路的上调。基线时上调病原体防御、白细胞介素和 T 细胞功能途径的患者对 NE 有部分缓解和更长的 OS。基线时上调细胞周期途径的患者在 NE 后表现为稳定/进展性疾病和较短的 OS。
NE 调节了 EGFRm NSCLC 的 TME。免疫相关途径的上调与更好的结果相关。
