Guo Yimeng, Jia Junting, Hao Zhiying, Yang Jing
Department of Pharmacy, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, China.
Front Pharmacol. 2023 Jun 20;14:1172969. doi: 10.3389/fphar.2023.1172969. eCollection 2023.
Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy. We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method. Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR) 0.55, 95% CI 0.45-0.67; HR 0.53, 95% CI 0.47-0.60; ORR: relative risk (RR) 1.50, 95% CI 1.32-1.71; RR 1.89, 95% CI 1.44-2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RR 1.12, 95% CI 1.03-1.21; RR 1.13, 95% CI 1.03-1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82-1.31), ORR (RR: 0.79, 95% CI 0.59-1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87-1.12), and AEs leading to death (RR 0.70, 95% CI 0.23-2.09). In progression-free survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy. The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy.
帕博利珠单抗和替雷利珠单抗在晚期非小细胞肺癌（NSCLC）的一线治疗中已显示出显著的临床益处。然而，尚无头对头临床试验比较过最佳选择。因此，我们进行了一项间接比较，以探索晚期NSCLC联合化疗的最佳选择。我们对随机试验进行了系统评价；临床结局包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和不良事件（AE）。采用布彻方法对替雷利珠单抗和帕博利珠单抗进行间接比较。数据从6项涉及2000多名参与者的随机试验中提取。直接荟萃分析表明，与单纯化疗相比，两种治疗方案均改善了临床结局（PFS：风险比（HR）0.55，95%置信区间0.45 - 0.67；HR 0.53，95%置信区间0.47 - 0.60；ORR：相对风险（RR）1.50，95%置信区间1.32 - 1.71；RR 1.89，95%置信区间1.44 - 2.48）。在安全性结局方面，替雷利珠单抗和帕博利珠单抗在3级或更高等级AE的发生率上有更高的风险（RR 1.12，95%置信区间1.03 - 1.21；RR 1.13，95%置信区间1.03 - 1.24）。间接比较显示，替雷利珠单抗联合化疗与帕博利珠单抗联合化疗在PFS（HR：1.04，95%置信区间0.82 - 1.31）、ORR（RR：0.79，95%置信区间0.59 - 1.07）、3级或更高等级AE的发生率（RR 0.99，95%置信区间0.87 - 1.12）以及导致死亡的AE（RR 0.70，95%置信区间0.23 - 2.09）方面无显著差异。在无进展生存期亚组分析中，结果表明替雷利珠单抗联合化疗与帕博利珠单抗联合化疗在PFS方面，按PD-L1 TPS表达水平、年龄、肝转移状态和吸烟状态划分均无显著差异。替雷利珠单抗联合化疗的疗效和安全性与帕博利珠单抗联合化疗无实质性差异。
