KEYNOTE-590: Long-term Outcomes of First-line Pembrolizumab, Chemotherapy for Advanced Esophageal Cancer

Manish A. Shah, MD, and colleagues are reporting 5-year follow-up data from the randomized, phase 3 KEYNOTE-590 study at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

KEYNOTE-590 enrolled 749 patients with locally advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus (ESCC), or Siewert type 1 gastroesophageal junction adenocarcinoma. They were randomized (1:1) to receive pembrolizumab (200 mg intravenously every 3 weeks for ≤35 cycles) plus chemotherapy (5-fluorouracil [≤35 cycles] and cisplatin [≤6 cycles]; n=373) or placebo plus chemotherapy (n=376).

The primary end points of the study were overall survival (OS) in patients with ESCC and a PD-L1 combined positive score (CPS) ≥10 as well as OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors v1.1 by investigator in all patients, patients with ESCC regardless of PD-L1 status, and patients in the intention-to-treat (ITT) population with CPS ≥10. Secondary end points included safety, among others.

Previous data from 22.6 months of follow-up in the KEYNOTE-590 study have shown that first-line pembrolizumab plus chemotherapy significantly improves survival compared with placebo plus chemotherapy in patients with advanced esophageal cancer.

After a median time from randomization to data cutoff of 58.8 months, 94.7% of patients discontinued treatment, mainly due to progressive disease (60.7%; n=449).

In the ITT population, the median OS was 12.3 months for patients receiving pembrolizumab and 9.8 months for those receiving placebo (hazard ratio [HR], 0.72; 95% CI, 0.62-0.84). Five-year OS rates were 10.6% and 3.0%, respectively.

Additionally, researchers reported the median PFS was 6.3 months for patients receiving pembrolizumab and 5.8 months for those receiving placebo (HR, 0.64; 95% CI, 0.54-0.75). Five-year PFS rates were 5.5% and 0%, respectively.

Grade 3-5 treatment-related adverse events (TRAEs) occurred in 71.9% of patients (n=266) in the pembrolizumab arm compared with 67.6% of patients (n=250) in the placebo arm. TRAEs led to death in 2.4% and 1.4% of patients, respectively.

“After 5 years, use of pembrolizumab plus chemotherapy showed durable efficacy versus placebo plus chemotherapy, with no new safety concerns, in patients with untreated advanced esophageal cancer,” Dr. Shah and colleagues concluded. “Long-term results continue to support first-line pembrolizumab plus chemotherapy for advanced esophageal cancer.”