Pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer: 5-year extended follow-up for the randomized phase III KEYNOTE-590 study
J-P. Metges, K. Kato, J-M. Sun, Lin Shen, Peter C. Enzinger, Antoine Adenis, Toshihiko Doi, Takashi Kojima, Z. Li, Sung‐Bae Kim, Byoung Chul Cho, Wasat Mansoor, SH Li, Patrapim Sunpaweravong, María Alsina, Gary L. Buchschacher, Hidenori Hara, A. Tsuji, Jimin Wu, Sukrut Shah, Pooja Bhagia, Manish A. Shah
Abstract
BACKGROUND: The global KEYNOTE-590 trial was the first to show a significant improvement in survival with immunotherapy plus chemotherapy in the first-line treatment of esophageal cancer (EC) and supported the approval of pembrolizumab plus chemotherapy in this setting. After a median follow-up of 22.6 months, pembrolizumab plus chemotherapy compared with placebo plus chemotherapy had a manageable safety profile and significantly improved survival of participants with previously untreated advanced EC. Results of a median follow-up of 58.8 months (range 49.2-70.6 months) are reported. PATIENTS AND METHODS: Adults with previously untreated advanced EC or Siewert type 1 gastroesophageal junction cancer were randomly assigned 1 : 1 to receive chemotherapy with or without pembrolizumab. Study outcomes were efficacy and safety. RESULTS: Overall, 749 participants received pembrolizumab plus chemotherapy (n = 373) or placebo plus chemotherapy (n = 376). Median overall survival was 12.3 months versus 9.8 months [hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.62-0.84] with pembrolizumab plus chemotherapy versus placebo plus chemotherapy; 5-year survival rates were 10.6% and 3.0%. Median progression-free survival (PFS) was 6.3 months versus 5.8 months (HR 0.64, 95% CI 0.54-0.75); 5-year PFS rates were 5.5% and not reached. Grade ≥3 treatment-related adverse events occurred in 71.9% and 67.6% of participants in the pembrolizumab plus chemotherapy and placebo plus chemotherapy groups, respectively. CONCLUSION: Data from KEYNOTE-590 continue to show durable efficacy after 5 years, and pembrolizumab plus chemotherapy more than tripled the 5-year overall survival rate compared with placebo plus chemotherapy, with no new safety signals. These results support first-line therapy with pembrolizumab plus chemotherapy as standard for previously untreated patients with advanced EC with programmed death-ligand 1 combined positive score ≥1.