Aim

The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab).

Methods

This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status.

Results

Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4–83.5) and 96.3% (95% CI 87.3–99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%).

Conclusions

SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer.

Trial registration

NCT03382600/JapicCTI-183829.

中文翻译：

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派姆单抗联合S-1加奥沙利铂作为一线治疗晚期胃/胃食管连接癌患者的安全性和有效性：KEYNOTE-659 IIb期研究的队列1数据

目标

KEYNOTE-659研究评估了pembrolizumab联合化学疗法作为日本晚期胃/胃食管连接（G / GEJ）癌症患者的一线治疗的有效性和安全性。在本文中，我们报告了队列1（S-1加奥沙利铂[SOX]和派姆单抗）的结果。

方法

这是一项针对晚期程序性死亡配体1（PD-L1）阳性，人类表皮生长因子受体2阴性的G / GEJ肿瘤的患者的非随机，多中心，开放标签IIb期研究。主要终点是通过盲人独立中央评价（BICR）评估的客观缓解率（ORR）。次要终点是反应持续时间（DOR），疾病控制率（DCR），反应时间（TTR），无进展生存期（PFS），总生存期（OS）和安全性。根据PD-L1合并阳性评分（CPS）状况进行探索性分析。

结果

评价了54名患者。中位随访时间为10.1个月。BICR的ORR和DCR分别为72.2％（95％置信区间[CI] 58.4-83.5）和96.3％（95％CI 87.3-99.5）。DOR，TTR，PFS和OS的中位数如下：未达到，1.5个月，9.4个月且未达到。CPS≥1至<10的患者的ORR为73.9％，CPS≥10的患者的ORR为71.0％。57.4％的患者报告了≥3级治疗相关不良事件（TRAE）。最常见的≥3级TRAEs减少血小板计数（14.8％），减少中性粒细胞计数（13.0％），结肠炎（5.6％）和肾上腺功能不全（5.6％）。

结论

SOX和pembrolizumab在晚期G / GEJ癌症的一线治疗中显示出令人鼓舞的疗效和可控的安全性。

试用注册

NCT03382600 / JapicCTI-183829。