Högner Anica, Thuss-Patience Peter
Campus Virchow-Klinikum, Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany.
Pharmaceuticals (Basel). 2021 Feb 12;14(2):151. doi: 10.3390/ph14020151.
Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.
免疫检查点抑制剂丰富了食管癌和胃癌的治疗格局。对于食管鳞状细胞癌（ESCC），选择性程序性死亡受体1（PD-1）抑制剂纳武利尤单抗在辅助治疗中可改善无病生存期（CHECKMATE-577）。在一线治疗中，ESCC患者联合化疗使用PD-1抑制剂帕博利珠单抗可使总生存期（OS）获益（KEYNOTE-590）。在二线治疗中，与化疗相比，纳武利尤单抗（ATTRACTION-03）和帕博利珠单抗（KEYNOTE-181）在OS方面显示出获益。这些数据使得纳武利尤单抗在欧洲、亚洲和美国被批准用于晚期ESCC患者的二线治疗，无论其程序性死亡配体1（PD-L1）状态如何；帕博利珠单抗在亚洲和美国被批准用于PD-L1联合阳性评分（CPS）≥10的患者。预计还会有更多批准。在胃食管交界癌和胃癌中，一线治疗中在化疗基础上加用纳武利尤单抗可改善PD-L1 CPS≥5的晚期疾病患者的OS（CHECKMATE-649）。此外，对于PD-L1 CPS≥1的患者，帕博利珠单抗在OS方面不劣于化疗（KEYNOTE-062）。在三线治疗中，纳武利尤单抗无论PD-L1表达如何均在OS方面显示出获益（ATTRACTION-02），已在亚洲获批；帕博利珠单抗可延长PD-L1阳性患者的缓解持续时间（KEYNOTE-059），已在美国获批。我们讨论了已完成的II期和III期临床试验的最新结果。
