对于转移性肿瘤患者停用免疫检查点抑制剂 (ICIs) 而非疾病进展 (PD) 的结果，目前的研究还很少。我们对所有报告因 PD 以外的原因停止 ICI 的患者临床结果的研究进行了荟萃分析。我们检索了 PubMed、Embase 和 Scopus 数据库，从每个数据库建立之初到 2023 年 12 月，寻找临床试验（随机或非随机） ）以及评估 PD-(L)1 和 CTLA-4 抑制剂对因 PD 以外原因停止治疗的转移性实体瘤患者的观察性研究。每项研究都必须提供游泳者图或 Kaplan-Meier 生存曲线，以便重建停止免疫治疗后的个体患者无进展生存期 (PFS) 数据。主要终点是自治疗停止之日起的总体无进展生存期（PFS），并根据肿瘤组织类型、治疗类型和停止原因而定。 Combersure 方法用于估计荟萃分析非参数总结生存曲线，假设研究水平存在随机效应。纳入了 36 项研究（2180 名患者）。汇总中位 PFS (mPFS) 为 24.7 个月（95% CI，18.8-30.6），12、24 和 36 个月时的 PFS 率分别为 69.8%（95% CI，63.1-77.3）、51.0%（95 % CI，43.4-59.8）和 34.0%（95% CI，27.0-42.9）。单变量分析显示，与非小细胞肺癌（NSCLC，13.5 个月）和肾细胞癌（RCC，10.0 个月）相比，黑色素瘤患者的 mPFS（43.0 个月）显着更长；层间比较检验 p-值 < 0.001);对于接受抗 PD-(L)1 抗 CTLA-4 治疗的患者与抗 PD-(L)1 单一疗法相比（44.6 个月与 19.9 个月；p 值 < 0.001），以及在 NSCLC 中，当治疗原因时与毒性发作相比，停药是选择性的（19.6 个月与 4.8 个月；p 值 = 0.003）。多变量分析证实了这些差异。因 PD 以外的原因停止 ICI 的患者的长期结局很大程度上受到临床病理特征的影响：黑色素瘤患者和/或接受抗 PD 治疗的患者停止治疗后的 PFS 较长。 L)1   抗 CTLA-4，RCC 患者或因毒性发作停止治疗的 NSCLC 患者的时间较短。意大利大学和研究部 (PRIN 2022Y7HHNW)。© 2024 作者。

The outcome of patients with metastatic tumors who discontinued immune checkpoint inhibitors (ICIs) not for progressive disease (PD) has been poorly explored. We performed a meta-analysis of all studies reporting the clinical outcome of patients who discontinued ICIs for reasons other than PD.We searched PubMed, Embase and Scopus databases, from the inception of each database to December 2023, for clinical trials (randomized or not) and observational studies assessing PD-(L)1 and CTLA-4 inhibitors in patients with metastatic solid tumors who discontinued treatment for reasons other than PD. Each study had to provide swimmer plots or Kaplan-Meier survival curves enabling the reconstruction of individual patient-level data on progression-free survival (PFS) following the discontinuation of immunotherapy. The primary endpoint was PFS from the date of treatment discontinuation overall and according to tumor histotype, type of treatment and reason of discontinuation. The Combersure's method was used to estimate meta-analytical non-parametric summary survival curves assuming random effects at study level.Thirty-six studies (2180 patients) were included. The pooled median PFS (mPFS) was 24.7 months (95% CI, 18.8-30.6) and the PFS-rate at 12, 24, and 36 months was respectively 69.8% (95% CI, 63.1-77.3), 51.0% (95% CI, 43.4-59.8) and 34.0% (95% CI, 27.0-42.9). Univariable analysis showed that the mPFS was significantly longer for patients with melanoma (43.0 months), as compared with non-small cell lung cancer (NSCLC, 13.5 months) and renal cell carcinoma (RCC, 10.0 months; between-strata comparison test p-value < 0.001); for patients treated with anti-PD-(L)1 + anti-CTLA-4 as compared with anti-PD-(L)1 monotherapy (44.6 versus 19.9 months; p-value < 0.001), and in NSCLC when the reason of treatment discontinuation was elective as compared with toxicity onset (19.6 versus 4.8 months; p-value = 0.003). The multivariable analysis confirmed these differences.The long-term outcome of patients who stopped ICIs for reasons other than PD was substantially affected by clinicopathological features: PFS after treatment discontinuation was longer in patients with melanoma, and/or treated with anti-PD-(L)1 + anti-CTLA-4, and shorter in patients with RCC or in those patients with NSCLC who stopped treatment for toxicity onset.The Italian Ministry of University and Research (PRIN 2022Y7HHNW).© 2024 The Authors.