帕博利珠单抗对比化疗用于 KEYNOTE-181 亚洲人群随机对照试验中的食管鳞癌患者。
Pembrolizumab versus chemotherapy for patients with esophageal squamous cell carcinoma enrolled in the randomized KEYNOTE-181 trial in Asia.
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
PLA Cancer Centre of Nanjing Bayi Hospital, Nanjing, China.
出版信息
ESMO Open. 2022 Feb;7(1):100341. doi: 10.1016/j.esmoop.2021.100341. Epub 2021 Dec 29.
BACKGROUND
In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study.
PATIENTS AND METHODS
Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level.
RESULTS
In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively.
CONCLUSIONS
Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.
背景
在随机 III 期 KEYNOTE-181 研究中，与化疗二线治疗相比，帕博利珠单抗延长了晚期食管癌和程序性死亡配体 1（PD-L1）联合阳性评分（CPS）≥10 的患者的总生存期（OS）。我们报告了 KEYNOTE-181 中入组的亚洲食管鳞状细胞癌（ESCC）患者的事后亚组分析，包括 KEYNOTE-181 中国扩展研究中的患者。
方法
340 名晚期/转移性 ESCC 亚洲患者入组 KEYNOTE-181，包括中国队列。患者按 1:1 随机分配接受帕博利珠单抗 200mg 每 3 周治疗≤2 年或研究者选择紫杉醇、多西他赛或伊立替康。未进行正式比较分析 OS、无进展生存期、缓解率和安全性。OS 根据 PD-L1 CPS 表达水平进行评估。
结果
在亚洲 ESCC 患者中，帕博利珠单抗组的中位 OS 为 10.0 个月，化疗组为 6.5 个月（风险比[HR]，0.63；95%CI 0.50-0.80；名义 P<0.0001）。帕博利珠单抗组中位无进展生存期为 2.3 个月，化疗组为 3.1 个月（HR，0.79；95%CI 0.63-0.99；名义 P=0.020）。帕博利珠单抗组客观缓解率为 17.1%，化疗组为 7.1%；中位缓解持续时间分别为 10.5 个月和 7.7 个月。在 PD-L1 CPS<1 肿瘤（帕博利珠单抗与化疗）的患者中，HR 为 0.99（95%CI 0.56-1.72）；PD-L1 CPS 截断值>1 的患者死亡风险更好[CPS≥1，0.57（0.44-0.75）；CPS≥5，0.56（0.41-0.76）；CPS≥10，0.53（0.37-0.75）]。帕博利珠单抗组 71.8%的患者和化疗组 89.8%的患者报告了治疗相关不良事件；帕博利珠单抗组和化疗组分别有 20.0%和 44.6%的患者报告了 3-5 级事件。
结论
帕博利珠单抗单药治疗在亚洲 ESCC 患者中显示出良好的疗效，与化疗相比，治疗相关不良事件更少。PD-L1 CPS≥1 是帕博利珠单抗在亚洲 ESCC 患者中疗效的合适截断值和预测标志物。
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