Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
Nat Commun. 2023 Aug 3;14(1):4655. doi: 10.1038/s41467-023-40349-z.
Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.
阿法替尼是一种不可逆的 ErbB 家族阻滞剂，可改善晚期表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLCm+）患者的生存。这项 II 期试验（NCT04201756）旨在评估新辅助阿法替尼治疗 III 期 NSCLCm+的可行性。47 例患者接受新辅助阿法替尼治疗（每日 40mg）。主要终点是客观缓解率（ORR）。次要终点包括病理完全缓解（pCR）率、病理降期率、无边缘切除（R0）率、无事件生存、无疾病生存、无进展生存、总生存、治疗相关不良事件（TRAEs）。ORR 为 70.2%（95%CI：56.5%至 84.0%），达到了预设终点。主要病理反应（MPR）、pCR、病理降期和 R0 率分别为 9.1%、3.0%、57.6%和 87.9%。中位生存期未达到。最常见的 TRAEs 是腹泻（78.7%）和皮疹（78.7%）。只有 3 例患者发生 3/4 级 TRAEs。生物标志物分析和肿瘤微环境动态的批量 RNA 测序被包括作为预先确定的探索性终点。CISH 表达是阿法替尼反应的一个有前途的标志物（AUC=0.918）。在应答者中，与基线样本相比，在治疗后肿瘤和淋巴结样本中分别观察到 T 细胞和 B 细胞相关特征增加。新辅助阿法替尼对 III 期 NSCLC+患者是可行的，并导致肿瘤微环境的动态变化。
