Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
Esophagus. 2024 Jul;21(3):306-318. doi: 10.1007/s10388-024-01053-z. Epub 2024 Apr 12.
BACKGROUND: First-line pembrolizumab plus chemotherapy (pembrolizumab-chemotherapy) demonstrated improved efficacy and a manageable safety profile versus placebo plus chemotherapy (placebo-chemotherapy) in the subgroup analysis of Japanese patients with advanced/metastatic esophageal cancer in KEYNOTE-590 at a median follow-up of 24.4 months. Longer-term data from the Japanese subgroup analysis of KEYNOTE-590 are reported. METHODS: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for ≤ 35 cycles plus chemotherapy (cisplatin 80 mg/m and 5-fluorouracil 800 mg/m/day). Endpoints included overall survival (OS) and progression-free survival (PFS; investigator-assessed per RECIST v1.1; dual primary) and safety (secondary). Early tumor shrinkage (ETS) and depth of response (DpR) were assessed post hoc. RESULTS: Overall, 141 patients were enrolled in Japan. As of July 9, 2021, median follow-up was 36.6 months (range, 29.8-45.7). Pembrolizumab-chemotherapy showed a trend toward favorable OS (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.47-1.03) and PFS (0.57; 0.39-0.83) versus placebo-chemotherapy. In the pembrolizumab-chemotherapy group, patients with ETS ≥ 20% (55/74; 74.3%) versus < 20% (19/74; 25.7%) had favorable OS (HR, 0.23; 95% CI 0.12-0.42) and PFS (0.24; 0.13-0.43). Patients with DpR ≥ 60% (31/74; 41.9%) versus < 60% (43/74; 58.1%) had favorable OS (HR, 0.37; 95% CI 0.20-0.68) and PFS (0.24; 0.13-0.43). Grade 3-5 treatment-related adverse events occurred in 55/74 patients (74.3%) with pembrolizumab-chemotherapy and 41/67 patients (61.2%) with placebo-chemotherapy. CONCLUSIONS: With longer-term follow-up of Japanese patients with advanced/metastatic esophageal cancer, efficacy continued to favor pembrolizumab-chemotherapy compared with placebo-chemotherapy, with no new safety signals observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03189719.
背景：在 KEYNOTE-590 中，经过 24.4 个月的中位随访，与安慰剂联合化疗（安慰剂-化疗）相比，一线帕博利珠单抗联合化疗（帕博利珠单抗-化疗）在晚期/转移性食管癌的日本患者亚组分析中显示出改善的疗效和可管理的安全性。本文报告了 KEYNOTE-590 日本亚组分析的更长期数据。
方法：患者按 1:1 随机分配，接受帕博利珠单抗 200 mg 或安慰剂，每 3 周一次，最多可使用 35 个周期，联合化疗（顺铂 80 mg/m2 和氟尿嘧啶 800 mg/m2/天）。主要终点包括总生存期（OS）和无进展生存期（PFS；研究者评估根据 RECIST v1.1；双重主要终点）和安全性（次要终点）。事后评估早期肿瘤退缩（ETS）和反应深度（DpR）。
结果：总体而言，共有 141 名日本患者入组。截至 2021 年 7 月 9 日，中位随访时间为 36.6 个月（范围，29.8-45.7）。与安慰剂-化疗相比，帕博利珠单抗-化疗显示出 OS（风险比[HR]，0.70；95%置信区间[CI]，0.47-1.03）和 PFS（0.57；0.39-0.83）的改善趋势。在帕博利珠单抗-化疗组中，ETS≥20%（55/74；74.3%）的患者与 ETS<20%（19/74；25.7%）的患者相比，OS（HR，0.23；95%CI，0.12-0.42）和 PFS（0.24；0.13-0.43）更好。DpR≥60%（31/74；41.9%）的患者与 DpR<60%（43/74；58.1%）的患者相比，OS（HR，0.37；95%CI，0.20-0.68）和 PFS（0.24；0.13-0.43）更好。55/74 例（74.3%）接受帕博利珠单抗-化疗的患者和 41/67 例（61.2%）接受安慰剂-化疗的患者发生 3-5 级治疗相关不良事件。
结论：在晚期/转移性食管癌的日本患者中进行更长时间的随访后，与安慰剂-化疗相比，帕博利珠单抗-化疗的疗效继续获益，未观察到新的安全性信号。
临床试验注册：ClinicalTrials.gov，NCT03189719。
N Engl J Med. 2022-2-3
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