Department of Clinical and Molecular Medicine, Sapienza, University of Rome, Policlinico Umberto I, Sant'Andrea Hospital, IDI IRCSS, Rome, Italy.
Instituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Pascale, Naples, Italy.
J Transl Med. 2020 Nov 25;18(1):446. doi: 10.1186/s12967-020-02588-2.
Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy.
We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial.
A total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407-2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719-0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763-0.997; P = 0.045).
The combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology.
针对 CTLA-4 和 PD-1 分子的伊匹单抗和纳武利尤单抗分别在几种类型的癌症中显示出疗效。尽管有这些结果，只有一小部分患者能保持持久的疗效。即使是伊匹单抗联合纳武利尤单抗，也在多种肿瘤类型中显示出显著的临床获益。然而，没有一项试验的主要终点设计是比较纳武利尤单抗联合伊匹单抗的疗效与纳武利尤单抗单药治疗的疗效。因此，伊匹单抗联合治疗的附加价值尚未明确。本研究的目的是证明联合治疗策略优于单药治疗。
我们对 2010 年至 2020 年期间发表的 I 期- II 期- III 期临床试验进行了荟萃分析，其中比较了伊匹单抗联合纳武利尤单抗与纳武利尤单抗单药治疗。我们根据每个试验的亚组分析提取了治疗的客观缓解率（ORR）、总生存期（OS）和无进展生存期（PFS）HR。
本荟萃分析共纳入 7 项试验。共有 1313 例患者接受了纳武利尤单抗联合伊匹单抗治疗，1110 例患者接受了纳武利尤单抗单药治疗。所有试验均报告了客观缓解率（ORR），研究之间没有异质性，汇总的优势比高度支持纳武利尤单抗联合伊匹单抗治疗优于纳武利尤单抗单药治疗（1.683；95%置信区间：1.407-2.012；P<0.0001）。有 3 项研究进行了无进展生存（PFS）分析，汇总的风险比有利于纳武利尤单抗联合伊匹单抗治疗优于纳武利尤单抗单药治疗（0.807；95%置信区间：0.719-0.907；P<0.0001）。只有 2 项试验考虑了总生存期（OS）终点，汇总的风险比也有利于纳武利尤单抗联合伊匹单抗治疗优于纳武利尤单抗单药治疗（0.87；95%置信区间：0.763-0.997；P=0.045）。
无论组织学类型如何，伊匹单抗联合纳武利尤单抗似乎优于纳武利尤单抗单药治疗癌症患者。
