First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study

IF 2.2 4区医学 Q3 GASTROENTEROLOGY & HEPATOLOGY Esophagus Pub Date : 2024-04-12 DOI:10.1007/s10388-024-01053-z

Ken Kato, Takashi Kojima, Hiroki Hara, Akihito Tsuji, Hisateru Yasui, Kei Muro, Taroh Satoh, Takashi Ogata, Ryu Ishihara, Masahiro Goto, Hideo Baba, Tomohiro Nishina, ShiRong Han, Keiichi Iwakami, Naoyoshi Yatsuzuka, Toshihiko Doi

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Abstract

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/m² and 5-fluorouracil 800 mg/m²/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.

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晚期/转移性食管癌的一线pembrolizumab联合化疗：3期KEYNOTE-590研究日本亚组的1年延长随访

背景在KEYNOTE-590日本晚期/转移性食管癌患者亚组分析中，一线pembrolizumab联合化疗（pembrolizumab-化疗）与安慰剂联合化疗（安慰剂-化疗）相比，在中位随访24.4个月时显示出更好的疗效和可控的安全性。本文报告了KEYNOTE-590日本亚组分析中的长期数据。方法将患者按1:1随机分配至pembrolizumab 200 mg或安慰剂，每3周一次，持续≤35个周期，同时进行化疗（顺铂80 mg/m2和5-氟尿嘧啶800 mg/m2/天）。终点包括总生存期（OS）和无进展生存期（PFS；根据 RECIST v1.1 由研究者评估；双重主要终点）和安全性（次要终点）。对早期肿瘤缩小（ETS）和反应深度（DpR）进行了事后评估。截至 2021 年 7 月 9 日，中位随访时间为 36.6 个月（29.8-45.7 个月）。与安慰剂-化疗相比，Pembrolizumab-化疗显示出良好的OS（危险比[HR]，0.70；95%置信区间[CI]0.47-1.03）和PFS（0.57；0.39-0.83）趋势。在pembrolizumab-化疗组中，ETS≥20%（55/74；74.3%）的患者与< 20%（19/74；25.7%）的患者相比，具有良好的OS（HR，0.23；95% CI 0.12-0.42）和PFS（0.24；0.13-0.43）。DpR≥60%（31/74；41.9%）与< 60%（43/74；58.1%）的患者具有良好的OS（HR，0.37；95% CI 0.20-0.68）和PFS（0.24；0.13-0.43）。结论通过对日本晚期/转移性食管癌患者的长期随访发现，与安慰剂化疗相比，pembrolizumab化疗的疗效仍然更佳，且未观察到新的安全性信号：临床试验注册：ClinicalTrials.gov，NCT03189719。

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来源期刊

Esophagus GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.90

自引率

8.30%

发文量

审稿时长

>12 weeks

期刊介绍： Esophagus, the official journal of the Japan Esophageal Society, introduces practitioners and researchers to significant studies in the fields of benign and malignant diseases of the esophagus. The journal welcomes original articles, review articles, and short articles including technical notes ( How I do it ), which will be peer-reviewed by the editorial board. Letters to the editor are also welcome. Special articles on esophageal diseases will be provided by the editorial board, and proceedings of symposia and workshops will be included in special issues for the Annual Congress of the Society.