■对转移性肿瘤患者停止免疫检查点抑制剂(ICIs)而不是进行性疾病(PD)的结果研究甚少。我们对所有报告因PD以外的原因停止ICI的患者的临床结果的研究进行了荟萃分析。
■我们搜索了PubMed,Embase和Scopus数据库,从每个数据库开始到2023年12月,用于临床试验(随机或不随机)和观察性研究,评估PD-(L)1和CTLA-4抑制剂在因PD以外的原因而停止治疗的转移性实体瘤患者中的应用.每个研究都必须提供游泳图或Kaplan-Meier存活曲线,以便在停止免疫疗法后重建无进展生存期(PFS)的个体患者水平数据。主要终点是治疗终止之日起总体PFS,根据肿瘤组织型,治疗类型和停药原因。Combersure方法用于估计荟萃分析非参数总结存活曲线,假设随机效应在研究水平。
■纳入36项研究(2180名患者)。合并的中位PFS(mPFS)为24.7个月(95%CI,18.8-30.6),12、24和36个月的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)。单变量分析显示黑色素瘤患者的mPFS显著延长(43.0个月),与非小细胞肺癌(NSCLC,13.5个月)和肾细胞癌(RCC,10.0个月;阶层间比较测试p值<0.001);对于使用抗PD-(L)1抗CTLA-4治疗的患者,与抗PD-(L)1单药治疗相比(44.6对19.9个月;p值<0.001),在NSCLC中,与毒性发作相比,停药的原因是选择性的(19.6对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ICIs的患者的长期结局受到临床病理特征的重大影响:黑色素瘤患者停止治疗后的PFS更长,和/或用抗PD-(L)1+抗CTLA-4治疗,并且在RCC患者或因毒性发作而停止治疗的NSCLC患者中更短。
■意大利大学研究部(PRIN2022Y7HNW)。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The Italian Ministry of University and Research (PRIN 2022Y7HHNW).