Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer

J Gastrointest Cancer. 2023 Sep;54(3):951-961. doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.

Abstract

Purpose: Pembrolizumab demonstrated antitumor activity in programmed death ligand 1 positive (combined positive score (CPS) ≥ 1) gastric/gastroesophageal junction cancer in KEYNOTE-059 (third line or beyond), KEYNOTE-061 (second line), and KEYNOTE-062 (first line). We characterized efficacy and safety of pembrolizumab monotherapy in Japanese patients across several lines of therapy in these studies.

Methods: This analysis was conducted in 34 patients from KEYNOTE-059 cohort 1 (all pembrolizumab), including 13 patients with CPS ≥ 1, 65 patients with CPS ≥ 1 from KEYNOTE-061 (pembrolizumab, n = 27; chemotherapy, n = 38), and 70 patients with CPS ≥ 1 from KEYNOTE-062 (pembrolizumab, n = 38; chemotherapy, n = 32). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated.

Results: In KEYNOTE-059, ORR with pembrolizumab was 9%, median PFS was 2 months, and median OS was 10 months. In KEYNOTE-061, median OS was 12 months with pembrolizumab versus 10 months with chemotherapy (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.39-1.15). Median PFS (pembrolizumab vs. chemotherapy) was 2 months versus 4 months (HR, 1.21; 95% CI, 0.69-2.13); ORR was 7% versus 18%. In KEYNOTE-062, median OS was 20 months with pembrolizumab versus 18 months with chemotherapy (HR, 0.76; 95% CI, 0.43-1.33). Median PFS (pembrolizumab vs. chemotherapy) was 6 months versus 7 months (HR, 1.03; 95% CI, 0.61-1.74); ORR was 29% versus 34%.

Conclusions: The current analysis provides valuable information that anti-PD-1 therapies are worthy of further assessment for gastric cancer.

Trial registration: ClinicalTrials.gov: NCT02335411 (KEYNOTE-059), NCT02370498 (KEYNOTE-061), and NCT02494583 (KEYNOTE-062).

Keywords: Biomarkers; Clinical trial; Gastrointestinal neoplasm; Japan; Pembrolizumab.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • East Asian People
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophagogastric Junction / pathology
  • Humans
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / therapy

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab

Associated data

  • ClinicalTrials.gov/NCT02370498
  • ClinicalTrials.gov/NCT02335411
  • ClinicalTrials.gov/NCT02494583