本研究的目的是探讨托瑞帕利单抗联合安罗替尼治疗曾经服用过表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）后出现耐药的晚期非小细胞肺癌（NSCLC）患者的疗效和安全性。纳入那些在一线或二线治疗中使用第一代或第二代EGFR-TKI而没有EGFR T790M突变的耐药患者，以及在一线或二线治疗中使用第三代EGFR-TKI后进展的患者。所有患者每3周接受托瑞帕利单抗（每天240毫克，静脉注射）联合安罗替尼（每天12毫克，第1-14天，口服）的治疗。治疗持续至疾病进展或毒性不可耐受为止。主要终点为由调查员评估的客观缓解率（ORR）。次要终点为无进展生存期（PFS）。总计自2020年5月至2021年10月期间纳入19名患者。ORR为0％，中位PFS为2.1个月（95％CI 0.251-3.949）。11％的患者发生了≥3级与治疗相关的不良事件（AE）。常见的不良事件包括甲状腺功能减退（12/19），疲劳（9/19）和高血压（8/19）。稳定病组的患者在入组前EGFR突变等位基因频率（AF）较进展病组低（p = 0.031）。没有检测到EGFR突变（EGFR-）的患者与带有EGFR突变的患者相比，PFS更长（p = 0.059）。基线时可溶性程序性细胞死亡配体1（PD-L1）水平高的患者也倾向于有更长的PFS（p = 0.160）。托瑞帕利单抗联合安罗替尼在之前未接受化疗的EGFR-TKI耐药晚期NSCLC患者中具有可耐受性。无检测到EGFR突变和高可溶性PD-L1水平的患者可能会从这种无化疗的治疗中获益。© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non-small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).Patients who developed resistance after using first- or second-generation EGFR-TKIs as their first-line regimen without EGFR T790M mutation or had disease progression after being treated with third-generation EGFR-TKIs as first- or second-line therapy were enrolled. All patients received toripalimab (240 mg/day on Day 1, intravenously) combined with anlotinib (12 mg/day, Days 1-14, orally) once every 3 weeks. Treatment continued until disease progression, or if toxicity was intolerable. The primary endpoint was the objective response rate (ORR) assessed by the investigator. The secondary endpoint was the progression-free survival (PFS).In total, 19 patients were enrolled between May 2020 and October 2021.The ORR was 0%, and a median PFS was 2.1 months (95% CI 0.251-3.949). Grade ≥3 treatment-related adverse events (AEs) occurred in 11% patients. Common adverse events included hypothyroidism (12/19), fatigue (9/19), and hypertension (8/19). Patients in stable disease (SD) group had lower abundance of EGFR mutation allele frequency (AF) before enrollment than those in progressive disease (PD) group (p = 0.031). Patients without detectable EGFR mutation (EGFR-) had longer PFS compared to the ones with EGFR mutations (p = 0.059). Patients with high levels of soluble programmed cell death ligand 1 (PD-L1) at baseline also tended to have longer PFS (p = 0.160).Toripalimab combined with anlotinib was tolerable in EGFR-TKI-resistant advanced NSCLC patients not previously treated with chemotherapy. Patients without detectable EGFR mutation and high soluble PD-L1 levels may benefit from this chemotherapy-free treatment.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.