Sanhome-CPU Joint Laboratory, China Pharmaceutical University, Nanjing, PR China.
Antibody Engineering Laboratory, School of Life Science & Technology, China Pharmaceutical University, Nanjing, PR China.
Immunopharmacol Immunotoxicol. 2021 Jun;43(3):386-394. doi: 10.1080/08923973.2021.1924195. Epub 2021 May 20.
Nivolumab and Ipilimumab are immune checkpoint inhibitors. The combination of Nivolumab and Ipilimumab has been reported to have complementary effects in the treatment of metastatic melanoma. The combination therapy of Nivolumab and Ipilimumab (N+I) has shown synergistic effects in cancer immunotherapy but this is still controversial due to the higher incidence of toxicity. Hence, we conducted a meta-analysis to evaluate the efficacy and safety profile of Nivolumab combined with Ipilimumab and compared the different dosing schedules of the N+I combination. By searching in PubMed, PMC, Cochrane library and major conference abstracts, eligible sixteen studies including N+I therapy and Nivolumab monotherapy were selected to analyze overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and high-grade (3-4) adverse effects (AEs). Compared with monotherapy of Nivolumab, N+I significantly improved ORR (RR=1.40 [95% CI 1.27, 1.54], P<0.00001) and PFS (Hazard Ratio (HR)=0.83 [95% CI 0.77, 0.90], P<0.00001), but not OS (HR=0.93 [95% CI 0.84, 1.03], P=0.16). In a sub-analysis, the combination of Nivolumab 1mg/kg plus Ipilimumab 3mg/kg (N1I3) and Nivolumab 3mg/kg plus Ipilimumab 1mg/kg (N3I1) achieved better ORR and PFS than Nivolumab 3mg/kg (N3) alone. Remarkably, OS was also prolonged with the N1I3 combination compared with the N3I1 combination or N3. Furthermore, a higher incidence of high-grade AEs also occurred with the combination therapy of N1I3. N+I combination therapy showed greater ORR and PFS compared with Nivolumab monotherapy. N1I3 combination provided the benefit of ORR, PFS and OS but was associated with a higher incidence of toxicity.
纳武利尤单抗和伊匹单抗是免疫检查点抑制剂。纳武利尤单抗和伊匹单抗联合应用在转移性黑色素瘤的治疗中具有互补作用。纳武利尤单抗和伊匹单抗联合治疗（N+I）在癌症免疫治疗中显示出协同作用，但由于毒性发生率较高，这仍然存在争议。因此，我们进行了一项荟萃分析，以评估纳武利尤单抗联合伊匹单抗的疗效和安全性，并比较了 N+I 联合治疗的不同剂量方案。通过在 PubMed、PMC、Cochrane 图书馆和主要会议摘要中进行检索，选择了 16 项符合条件的研究，包括 N+I 治疗和纳武利尤单抗单药治疗，以分析总缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和高级（3-4 级）不良事件（AE）。与纳武利尤单抗单药治疗相比，N+I 显著提高了 ORR（RR=1.40[95%CI 1.27,1.54]，P<0.00001）和 PFS（风险比（HR）=0.83[95%CI 0.77,0.90]，P<0.00001），但对 OS 没有影响（HR=0.93[95%CI 0.84,1.03]，P=0.16）。在亚分析中，纳武利尤单抗 1mg/kg 加伊匹单抗 3mg/kg（N1I3）和纳武利尤单抗 3mg/kg 加伊匹单抗 1mg/kg（N3I1）的组合比纳武利尤单抗 3mg/kg（N3）单药治疗获得更好的 ORR 和 PFS。值得注意的是，与 N3I1 联合治疗或 N3 相比，N1I3 联合治疗也延长了 OS。此外，N1I3 联合治疗还导致更高的高级 AE 发生率。与纳武利尤单抗单药治疗相比，N+I 联合治疗显示出更大的 ORR 和 PFS。N1I3 联合治疗在提供 ORR、PFS 和 OS 获益的同时，也与更高的毒性发生率相关。
