Abstract
Abstract
Background
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.
Methods
Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/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.
Results
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%.
Conclusion
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.
Clinical trial registry
ClinicalTrials.gov, NCT03189719.
Funder
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
Publisher
Springer Science and Business Media LLC
Reference20 articles.
1. Ferlay J, Ervik M, Lam F et al. Global cancer observatory: cancer today. 2018. https://gco.iarc.fr/today. Accessed 10 July 2019.
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
3. Kitagawa Y, Uno T, Oyama T, et al. Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: part 1. Esophagus. 2019;16(1):1–24.
4. Tanaka Y, Yoshida K, Suetsugu T, Imai T, Matsuhashi N, Yamaguchi K. Recent advancements in esophageal cancer treatment in Japan. Ann Gastroenterological Surg. 2018;2(4):253–65.
5. Merck’s KEYTRUDA® (pembrolizumab) Receives Two New Approvals in Japan. News release. Published 24 August 2020. https://www.merck.com/news/mercks-keytruda-pembrolizumab-receives-two-new-approvals-in-japan/. Accessed 23 May 2022.