Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
Esophagus. 2022 Oct;19(4):683-692. doi: 10.1007/s10388-022-00920-x. Epub 2022 Jun 7.
The phase 3 KEYNOTE-590 (NCT03189719) study showed first-line pembrolizumab plus chemotherapy significantly prolonged overall survival and progression-free survival versus placebo plus chemotherapy in patients with advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction. We describe a subgroup analysis of Japanese patients from KEYNOTE-590.
Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo plus chemotherapy (cisplatin 80 mg/m and 5-fluorouracil 800 mg/m/day). Efficacy was evaluated in all Japanese patients and those with esophageal squamous cell carcinoma and programmed death ligand 1 combined positive score ≥ 10. Dual primary endpoints were overall survival and progression-free survival per RECIST v1.1 by investigator. Secondary endpoints included objective response rate per RECIST v1.1 by investigator and safety and tolerability.
At data cutoff (July 2, 2020), 141 Japanese patients were randomly assigned (pembrolizumab plus chemotherapy, 74; placebo plus chemotherapy, 67). In all Japanese patients, median overall survival was 17.6 months with pembrolizumab plus chemotherapy versus 11.7 months with chemotherapy (hazard ratio, 0.71; 95% confidence interval, 0.47-1.09), median progression-free survival was 6.3 versus 6.0 months (hazard ratio, 0.58; 95% confidence interval, 0.40-0.84), and objective response rate was 56.8% versus 38.8%. Grade 3-5 treatment-related adverse events were 74.3% and 61.2%.
First-line pembrolizumab plus chemotherapy demonstrated improvement in overall survival and progression-free survival compared with placebo plus chemotherapy in Japanese patients with advanced/metastatic esophageal cancer; safety was comparable between treatment groups.
ClinicalTrials.gov, NCT03189719.
III 期 KEYNOTE-590 研究（NCT03189719）表明，与安慰剂加化疗相比，一线帕博利珠单抗加化疗可显著延长晚期不可切除或转移性食管腺癌或食管鳞状细胞癌患者以及晚期/转移性食管胃结合部 Siewert Ⅰ型腺癌患者的总生存期和无进展生存期。我们描述了 KEYNOTE-590 中日本患者的亚组分析。
符合条件的患者按 1:1 随机分配至帕博利珠单抗 200mg 静脉输注每 3 周一次或安慰剂加化疗（顺铂 80mg/m2 和氟尿嘧啶 800mg/m2/天）。在所有日本患者和那些具有程序性死亡配体 1 联合阳性评分≥10 的患者中评估疗效。主要终点为研究者评估的 RECIST v1.1 总生存期和无进展生存期。次要终点包括研究者评估的 RECIST v1.1 客观缓解率和安全性及耐受性。
数据截止（2020 年 7 月 2 日）时，141 例日本患者被随机分配（帕博利珠单抗加化疗组 74 例，安慰剂加化疗组 67 例）。在所有日本患者中，帕博利珠单抗加化疗组的中位总生存期为 17.6 个月，化疗组为 11.7 个月（风险比，0.71；95%置信区间，0.47-1.09），中位无进展生存期为 6.3 个月与 6.0 个月（风险比，0.58；95%置信区间，0.40-0.84），客观缓解率为 56.8%与 38.8%。3-5 级治疗相关不良事件分别为 74.3%和 61.2%。
与安慰剂加化疗相比，一线帕博利珠单抗加化疗可改善晚期/转移性食管癌日本患者的总生存期和无进展生存期；两组间安全性相当。
ClinicalTrials.gov，NCT03189719。
