Department of VIP region, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China.
Int Immunopharmacol. 2022 Aug;109:108790. doi: 10.1016/j.intimp.2022.108790. Epub 2022 Apr 30.
Different clinical trials for advanced esophageal cancer have investigated diverse immuno-oncology combinational treatment in first-line setting, but the optimal choice has not been identified.
We used PubMed, Embase, and Cochrane Library databases for systematic retrieval. The primary endpoint was overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs) between immune checkpoint inhibitors combined with chemotherapy and chemotherapy.
A total of five phase-III randomized controlled trials involving 3,163 patients met the inclusion criteria. Significantly improved OS (HR: 0.69, 95% CI: 0.62-0.76, P＜0.001), PFS (HR: 0.62, 95% CI: 0.55-0.70, P < 0.001) and ORR (RR: 1.41, 95% CI: 1.23-1.62, P＜0.001) were observed when programmed death 1 (PD-1) inhibitor was added to chemotherapy. Toripalimab plus chemotherapy achieved the best OS benefit than any other treatment examined (HR: 0.58, 95% CI: 0.43-0.78). The longest PFS was founded in both sintilimab-chemotherapy and camrelizumab-chemotherapy combination (HR: 0.56, 95% CI: 0.46-0.68). Patients treated with nivolumab-chemotherapy got the best ORR improvement as compared to other combinations (RR: 1.73, 95% CI:1.40-2.14). Camrelizumab-chemotherapy and pembrolizumab-chemotherapy caused a relatively lower incidence of grade ≥ 3 AEs than other immunotherapy combination regimens. Subgroup analyses suggested significant OS advantage in programmed death-ligand 1(PD-L1) tumor-positive score (TPS) ≥ 10% groups and obviously longer PFS in PD-L1 combined positive score (CPS) ≥ 10 groups.
In advanced esophageal cancer, PD-1 inhibitors combined with chemotherapy as first-line therapy have better survival outcomes than chemotherapy with greater but manageable toxicity. Toripalimab-chemotherapy showed the best OS benefit over chemotherapy, while sintilimab-chemotherapy and camrelizumab-chemotherapy generated the best PFS. The highest ORR improvement was founded in patients receiving nivolumab plus chemotherapy.
不同的晚期食管癌临床试验在一线治疗中研究了多种免疫肿瘤联合治疗，但尚未确定最佳选择。
我们使用 PubMed、Embase 和 Cochrane Library 数据库进行系统检索。主要终点是免疫检查点抑制剂联合化疗与化疗相比的总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和治疗相关不良反应（AE）。
共有 5 项纳入 3163 例患者的 III 期随机对照试验符合纳入标准。与化疗相比，PD-1 抑制剂联合化疗可显著改善 OS（HR：0.69，95%CI：0.62-0.76，P＜0.001）、PFS（HR：0.62，95%CI：0.55-0.70，P＜0.001）和 ORR（RR：1.41，95%CI：1.23-1.62，P＜0.001）。与其他检查的任何治疗相比，特瑞普利单抗联合化疗的 OS 获益最佳（HR：0.58，95%CI：0.43-0.78）。最长的 PFS 分别见于信迪利单抗联合化疗和卡瑞利珠单抗联合化疗（HR：0.56，95%CI：0.46-0.68）。与其他联合方案相比，纳武利尤单抗联合化疗患者的 ORR 改善最佳（RR：1.73，95%CI：1.40-2.14）。卡瑞利珠单抗联合化疗和帕博利珠单抗联合化疗引起的 3 级及以上 AE 发生率相对较低。亚组分析表明，PD-L1 肿瘤阳性评分（TPS）≥10%的患者 OS 优势显著，PD-L1 联合阳性评分（CPS）≥10 的患者 PFS 明显更长。
在晚期食管癌中，PD-1 抑制剂联合化疗作为一线治疗较化疗有更好的生存获益，但毒性更大但可管理。特瑞普利单抗联合化疗的 OS 获益最佳，信迪利单抗联合化疗和卡瑞利珠单抗联合化疗的 PFS 最佳。接受纳武利尤单抗联合化疗的患者 ORR 改善最明显。
