First-Line Pembrolizumab Plus Chemotherapy for HER2-Negative Advanced Gastric Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-859 Study
Shukui Qin, Yuxian Bai, Jin Li, Hongming Pan, Suxia Luo, Yanli Qu, Feng Ye, Lin Yang, Tianshu Liu, Wei Li, Xi Chen, Jianwei Yang, Jieer Ying, Xiaoyan Lin, Lin Zhao, Xinjun Liang, Yixiang Mao, Run Guo, Yi Zuo, Sonal Bordia, Shouguo Li
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引用次数: 0
Abstract
Introduction
Results of the global, randomized, phase 3 KEYNOTE-859 study (N = 1579) showed that first-line pembrolizumab plus chemotherapy produced a statistically significant and clinically meaningful improvement in overall survival (OS) with manageable toxicity versus placebo plus chemotherapy in patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)–negative gastric or gastroesophageal junction cancer. This subgroup analysis was conducted to investigate outcomes in patients enrolled in mainland China.
Methods
Adults with previously untreated advanced or metastatic HER2-negative gastric cancer or gastroesophageal junction adenocarcinoma were randomly assigned (1:1) to receive pembrolizumab or placebo with fluoropyrimidine- and platinum-containing chemotherapy. The primary outcome was OS. Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), all assessed per RECIST v1.1 by blinded independent central review, and safety.
Results
Overall, 236 patients were enrolled in mainland China (126 pembrolizumab plus chemotherapy; 110 placebo plus chemotherapy). Median time from randomization to database cutoff (October 3, 2022) was 24.7 months (range 15.3–38.9). Median OS was 15.9 months (95% confidence interval [CI] 13.2–19.2) for pembrolizumab plus chemotherapy versus 12.2 months (95% CI 10.6–14.1) for placebo plus chemotherapy (hazard ratio [HR], 0.68; 95% CI 0.50–0.91). Median PFS was 8.1 months (95% CI 6.9–9.6) for pembrolizumab plus chemotherapy versus 5.7 months (95% CI 4.5–6.5) for placebo plus chemotherapy (HR, 0.65; 95% CI 0.48–0.88). ORR was 69.0% for pembrolizumab plus chemotherapy versus 45.5% for placebo plus chemotherapy; median DOR was 8.2 months (range 1.2+ to 34.6+) versus 5.5 months (range 1.3+ to 31.2+), respectively. Grade 3–5 treatment-related adverse events occurred in 82 patients (65.6%) treated with pembrolizumab plus chemotherapy and 54 patients (49.1%) treated with placebo plus chemotherapy.
Conclusion
Consistent with efficacy in the overall population from KEYNOTE-859, first-line pembrolizumab plus chemotherapy showed improved efficacy, versus placebo plus chemotherapy, and manageable safety in patients enrolled in mainland China.
全球随机3期KEYNOTE-859研究（N = 1579）的结果显示，与安慰剂加化疗相比，一线派姆单抗加化疗对局部晚期或转移性人表皮生长因子受体2 （HER2）阴性胃癌或胃食管结癌患者的总生存期（OS）有统计学意义和临床意义的改善，且毒性可控。本亚组分析旨在调查中国大陆入组患者的预后。方法：先前未经治疗的晚期或转移性her2阴性胃癌或胃食管交界处腺癌的成人随机分配（1:1），接受派姆单抗或安慰剂联合含氟嘧啶和含铂化疗。主要结果是OS。次要结局包括无进展生存期（PFS）、客观缓解率（ORR）和缓解持续时间（DOR），所有这些都是通过盲法独立中心审查根据RECIST v1.1进行评估的，以及安全性。结果：中国大陆共纳入236例患者(126例派姆单抗+化疗；110安慰剂加化疗)。从随机化到数据库截止（2022年10月3日）的中位时间为24.7个月（范围15.3-38.9）。派姆单抗加化疗的中位OS为15.9个月（95%可信区间[CI] 13.2-19.2），安慰剂加化疗的中位OS为12.2个月（95% CI 10.6-14.1）(风险比[HR]， 0.68；95% ci 0.50-0.91)。派姆单抗加化疗的中位PFS为8.1个月（95% CI 6.9-9.6），而安慰剂加化疗的中位PFS为5.7个月（95% CI 4.5-6.5） (HR, 0.65；95% ci 0.48-0.88)。派姆单抗加化疗的ORR为69.0%，安慰剂加化疗的ORR为45.5%；中位DOR分别为8.2个月（1.2+至34.6+）和5.5个月（1.3+至31.2+）。在82例（65.6%）使用派姆单抗联合化疗的患者和54例（49.1%）使用安慰剂联合化疗的患者中发生了3-5级治疗相关不良事件。结论：与KEYNOTE-859在总体人群中的疗效一致，一线派姆单抗加化疗在中国大陆入组患者中比安慰剂加化疗显示出更高的疗效和可控的安全性。试验注册：Clinicaltrials.gov: NCT03675737。
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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