Division of Life Sciences and Medicine, Department of Oncology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
Division of Life Sciences and Medicine, Department of Ultrasound, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
Cancer Med. 2024 Oct;13(20):e70324. doi: 10.1002/cam4.70324.
Immune checkpoint inhibitors (ICIs) have drastically shifted the current landscape toward a wide variety of malignancies. However, ICIs are interrupted owing immune-related adverse events (irAEs), therapy completion, and disease progression. The risk-benefit of rechallenged ICIs remains inconclusive. Herein, a systematic review and meta-analysis were conducted to evaluate the safety and efficacy of ICI rechallenge in the treatment of advanced solid tumor.
PubMed, Web of Science, Embase, and Cochrane Library were searched to analyze the efficacy and safety of ICI rechallenge. The study protocol was approved by the PROSPERO International Register of Systematic Reviews (CRD42022372222). The last updated search date was March 2, 2024. Objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence rates of all- and high-grade irAEs were evaluated.
A total of 41 retrospective studies comprising 2343 patients were ultimately enrolled for qualitative and quantitative assessments. A total of 1200 (51.2%) individuals were male and the median age was 66 years (range 18-97 years). The majority of the tumors was lung cancer (n = 898, 38.3%). The occurrence rates of all-grade and high-grade (grade 3 or 4) irAEs between initial and readministration ICIs were not significantly different (all-grade: OR, 0.75, 95% CI: 0.39-1.45, p = 0.40; I = 87%; high-grade: OR, 0.96, 95% CI: 0.62-1.49, p = 0.87, I = 65%). ICIs restart presented a decreased ORR and DCR compared to initial ICI administration (ORR: OR, 0.36, 95% CI: 0.23-0.56, p < 0.00001; I = 67%; DCR: OR, 0.62, 95% CI: 0.43-0.89, p = 0.010; I = 53%). Seven studies with 513 patients for survival analysis revealed a nonsignificant difference in OS between the ICIs rechallenge and discontinuation cohorts (hazard ratio [HR]: 0.68, 95% confidence interval (CI): 0.35 to 1.35, p = 0.27).
Rechallenging immunotherapy is feasible, and patients should be carefully evaluated by a multidisciplinary team prior to initial therapy for close monitoring and assessment of the risk-benefit ratio. Therefore, prospective trials are essential to guide clinicians in the decision-making process. PROSPERO Registration: CRD42022372222.
免疫检查点抑制剂（ICIs）极大地改变了当前各种恶性肿瘤的治疗格局。然而，由于免疫相关不良事件（irAEs）、治疗完成和疾病进展，ICI 治疗被中断。重新使用 ICI 的风险效益仍不确定。本文进行了系统评价和荟萃分析，以评估 ICI 重新挑战治疗晚期实体瘤的安全性和疗效。
检索 PubMed、Web of Science、Embase 和 Cochrane Library 以分析 ICI 重新挑战的疗效和安全性。该研究方案已获得 PROSPERO 国际系统评价注册（CRD42022372222）的批准。最后一次更新搜索日期为 2024 年 3 月 2 日。评估了客观缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）以及所有和高等级 irAEs 的发生率。
最终纳入了 41 项回顾性研究，共 2343 名患者进行定性和定量评估。共有 1200 名（51.2%）患者为男性，中位年龄为 66 岁（范围 18-97 岁）。大多数肿瘤为肺癌（n=898，38.3%）。初始 ICI 和重新使用 ICI 之间的所有等级和高等级（3 级或 4 级）irAEs 的发生率没有显著差异（所有等级：OR，0.75，95%CI：0.39-1.45，p=0.40；I=87%；高等级：OR，0.96，95%CI：0.62-1.49，p=0.87，I=65%）。与初始 ICI 给药相比，ICI 重新开始治疗的 ORR 和 DCR 降低（ORR：OR，0.36，95%CI：0.23-0.56，p<0.00001；I=67%；DCR：OR，0.62，95%CI：0.43-0.89，p=0.010；I=53%）。7 项纳入 513 名患者的生存分析研究显示，ICI 重新挑战组和停药组的 OS 无显著差异（HR：0.68，95%CI：0.35 至 1.35，p=0.27）。
重新挑战免疫疗法是可行的，患者在首次治疗前应通过多学科团队进行仔细评估，以便密切监测和评估风险效益比。因此，前瞻性试验对于指导临床医生的决策过程至关重要。PROSPERO 注册：CRD42022372222。
