Yang Jin, Zeng Ran, Zhou Jianping, Luo Lifeng, Lyu Mengchen, Liu Fang, Sun Xianwen, Zhou Ling, Wang Xiaofei, Bao Zhiyao, Chen Wei, Dumoulin Daphne W, Gao Beili, Xiang Yi
Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Transl Lung Cancer Res. 2022 Jun;11(6):1038-1050. doi: 10.21037/tlcr-22-360.
The rechallenge of immune checkpoint inhibitors (ICI) is now an optional strategy for patients who discontinued ICI due to immune-related adverse events (irAEs) or disease progression. However, little data is available for the prognosis and prognostic factors of patients receiving ICI rechallenge treatment in advanced lung cancer patients. Our study aimed to explore the efficacy, prognosis and safety of patients who received anti-programmed cell death-1/programmed cell death ligand 1 (anti-PD-1/PD-L1) inhibitor rechallenge.
In our retrospective cohort study, data of advanced lung cancer patients who received anti-PD-1/PD-L1 inhibitor and discontinued due to irAEs or disease progression were collected from December 2016 to August 2021. Enrolled patients were categorized into two groups: rechallenge group (R group) and non-rechallenge group (NR group). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety data were analyzed. Cox model and subgroup analysis were analyzed according to baseline characteristics, ICI type, the reason for discontinuing ICI, etc. According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), evaluation was performed routinely every 6-8 weeks after initiating treatment with the PD-1/PD-L1 inhibitor. The last follow-up in the study was on September 20, 2021.
Eighty-one patients who met our inclusion criteria were enrolled. In the whole cohort, the R group achieved better OS than the NR group [hazard ratio (HR) =0.176; 95% confidence interval (CI): 0.065-0.477; P=0.001). In the irAEs group, the survival analyses showed a trend toward improved OS in the rechallenge subgroup (HR =0.287; 95% CI: 0.081-1.025; P=0.055), and a promising DCR of 75% after an ICI rechallenge. Additionally, the exploration of safety outcomes indicated an acceptable recurrence rate (22.5%) of irAEs and an early onset of irAEs after an ICI rechallenge. In the disease progression group, the rechallenge subgroup did not improve OS (HR =0.214; 95% CI: 0.027-1.695; P=0.144), and the DCR of the rechallenge subgroup was 40% after ICI rechallenge.
ICI rechallenge might be an attractive option for patients who discontinue treatment due to irAEs. For patients with disease progression, further research should be conducted. The recurrence of irAEs and their early onset during the second round of ICI should be considered.
免疫检查点抑制剂（ICI）再挑战目前是因免疫相关不良事件（irAE）或疾病进展而停用ICI的患者的一种可选策略。然而，关于晚期肺癌患者接受ICI再挑战治疗的预后及预后因素的数据很少。我们的研究旨在探讨接受抗程序性细胞死亡蛋白1/程序性死亡配体1（抗PD-1/PD-L1）抑制剂再挑战患者的疗效、预后和安全性。
在我们的回顾性队列研究中，收集了2016年12月至2021年8月期间接受抗PD-1/PD-L1抑制剂并因irAE或疾病进展而停药的晚期肺癌患者的数据。纳入的患者分为两组：再挑战组（R组）和非再挑战组（NR组）。分析无进展生存期（PFS）、总生存期（OS）、疾病控制率（DCR）和安全性数据。根据基线特征、ICI类型、停用ICI的原因等进行Cox模型和亚组分析。根据实体瘤疗效评价标准第1.1版（RECIST 1.1），在开始使用PD-1/PD-L1抑制剂治疗后每6-8周进行常规评估。本研究的最后随访时间为2021年9月20日。
81例符合我们纳入标准的患者入组。在整个队列中，R组的OS优于NR组[风险比（HR）=0.176；95%置信区间（CI）：0.065-0.477；P=0.001]。在irAE组中，生存分析显示再挑战亚组的OS有改善趋势（HR =0.287；95%CI：0.081-1.025；P=0.055），ICI再挑战后的DCR有望达到75%。此外，安全性结果探索表明irAE的复发率可接受（22.5%），且ICI再挑战后irAE出现较早。在疾病进展组中，再挑战亚组未改善OS（HR =0.214；95%CI：0.027-1.695；P=0.144），ICI再挑战后再挑战亚组的DCR为40%。
ICI再挑战可能是因irAE而停药患者的一个有吸引力的选择。对于疾病进展的患者，应进行进一步研究。应考虑irAE的复发及其在第二轮ICI治疗期间的早期发作。
