Jin Yao, Wei Jiayan, Weng Yiming, Feng Jia, Xu Zexi, Wang Peiwei, Cui Xue, Chen Xinyi, Wang Jinsong, Peng Min
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
Front Oncol. 2022 Feb 25;12:732814. doi: 10.3389/fonc.2022.732814. eCollection 2022.
Immune checkpoint inhibitors (ICIs) have made a breakthrough in the systemic treatment of patients with advanced tumors. However, little is known about their efficacy and safety in adjuvant settings after the resection of solid tumors.
We performed a meta-analysis on the efficacy and safety of programmed death 1 (PD1)/PD-1 ligand (PDL1) inhibitors in adjuvant therapy after tumor resection using Review Manager 5.3, based on published clinical studies. The outcomes included recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and adverse events (AEs).
Eight randomized controlled trials (RCTs) were included in the analysis. The use of PD1/PDL1 inhibitors in adjuvant therapy significantly improved RFS (hazard ratio [HR] = 0.72; 95% confidence interval [CI] 0.67-0.78, p < 0.00001). However, there was no statistically significant difference in OS between PD1/PDL1 inhibitors and placebo (HR = 0.86; 95% CI 0.74-1.00, p = 0.05). Gender, age, and PDL1 status were independent predictors of RFS with PD1/PDL1 inhibitors. As for the safety analysis results, PD1/PDL1 inhibitors had a higher incidence of fatigue (risk ratio [RR] = 1.22; 95% CI 1.01-1.49, p = 0.04), nausea (RR = 1.47; 95% CI 1.11-1.94, p = 0.007), and pruritus (RR = 1.96; 95% CI 1.57-2.44, p < 0.00001). In addition, the incidence of any grade adverse events increased in the PD1/PDL1 inhibitor group (RR = 1.03; 95% CI 1.02-1.05, p < 0.0001).
This is the first meta-analysis on the efficacy and safety of PD1/PDL1 inhibitors in adjuvant therapy. The use of PD1/PDL1 inhibitors in adjuvant therapy could significantly reduce the recurrence rate after solid tumor resection. However, the incidence of fatigue, nausea, pruritus, and any grade AEs also increased, which should be monitored with vigilance.
免疫检查点抑制剂（ICIs）在晚期肿瘤患者的全身治疗方面取得了突破。然而，对于其在实体瘤切除术后辅助治疗中的疗效和安全性知之甚少。
我们使用Review Manager 5.3，基于已发表的临床研究，对程序性死亡1（PD1）/PD-1配体（PDL1）抑制剂在肿瘤切除术后辅助治疗中的疗效和安全性进行了荟萃分析。结局指标包括无复发生存期（RFS）、无病生存期（DFS）、总生存期（OS）和不良事件（AEs）。
分析纳入了8项随机对照试验（RCT）。在辅助治疗中使用PD1/PDL1抑制剂可显著改善RFS（风险比[HR]=0.72；95%置信区间[CI]0.67-0.78，p<0.00001）。然而，PD1/PDL1抑制剂与安慰剂组在OS方面无统计学显著差异（HR=0.86；95%CI 0.74-1.00，p=0.05）。性别、年龄和PDL1状态是使用PD1/PDL1抑制剂时RFS的独立预测因素。至于安全性分析结果，PD1/PDL1抑制剂出现疲劳的发生率更高（风险比[RR]=1.22；95%CI 1.01-1.49，p=0.04）、恶心（RR=1.47；95%CI 1.11-1.94，p=0.007）和瘙痒（RR=1.96；95%CI 1.57-2.44，p<0.00001）。此外，PD1/PDL1抑制剂组任何级别的不良事件发生率均有所增加（RR=1.03；95%CI 1.02-1.05，p<0.0001）。
这是关于PD1/PDL1抑制剂在辅助治疗中疗效和安全性的首个荟萃分析。在辅助治疗中使用PD1/PDL1抑制剂可显著降低实体瘤切除术后的复发率。然而，疲劳、恶心、瘙痒及任何级别的不良事件发生率也有所增加，应予以密切监测。
