FDA Approves Pembrolizumab Plus Chemotherapy to Treat Metastatic HER2-Negative Gastric, Gastroesophageal Junction Adenocarcinoma


The approval makes pembrolizumab the first-line treatment for individuals with this cancer.

The FDA has approved pembrolizumab (Keytruda, Merck) in combination with fluoropyrimidine and platinum-containing chemotherapy to treat individuals with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Human intestines colon organ shape. Digestive tract problems colitis or colon cancer - Image credit: 9dreamstudio | stock.adobe.com

Image credit: 9dreamstudio | stock.adobe.com

Gastric stomach cancer is reported to develop gradually over many years and does not show signs of symptoms early on. This results in about 70% individuals being diagnosed at the advanced stage of the disease. About 90% to 95% of gastric cancers are deemed adenocarcinomas, which are developed from the cells in the innermost lining of the stomach. However, the 5-year survival rate for individuals diagnosed at the advanced stage of gastric cancer is only 6%. Researchers have estimated that in the United States, 11,000 deaths will occur among individuals with the disease in 2023.

As an anti-programmed death receptor-1 (PD-1) therapy, pembrolizumab is designed to increase the ability of the body’s immune system to detect and fight the tumor cells. The 100 mg injection contains a humanized monoclonal antibody to block the interaction of the PD-1 and the ligands— PD-L1 and PD-L2. This should then activate the T lymphocytes that could impact the tumor cells and the healthy cells.

The press release noted that the approval was granted based on the Phase 3 KEYNOTE-859 randomized, double-blind, placebo-controlled trial that compared pembrolizumab in combination with luoropyrimidine- and platinum-containing chemotherapy to a placebo in combination with chemotherapy.

About the KEYNOTE-859 Trial

Trial name: KEYNOTE-859

Clinicaltrials.gov ID: NCT03675737

Sponsor: Merck

Completion Date: September 28, 2024 (estimated)

The trial included 1579 individuals with HER2-negative advanced gastric or GEJ adenocarcinoma, who did not receive treatment for metastatic disease in the past.

The press release noted that the major efficacy outcome measure was overall survival (OS) and the secondary outcome measures included progression-free survival (PFS), objective response rate (ORR) and duration of response.

The researchers found that OS, PFS, and ORR were improved in individuals that received pembrolizumab and chemotherapy, compared to chemotherapy alone.

The data confirmed that pembrolizumab combined with chemotherapy reduced death by 22% and the median overall survival rate was 12.9 months, compared to 11.5 months for individuals that only received chemotherapy.

“The majority of patients with gastric cancer are diagnosed at an advanced stage, at which point they face a poor prognosis with a 5-year survival rate of 6%,” said Zev A. Wainberg, MD, professor of medicine at University of California, Los Angeles School of Medicine and co-director of the UCLA GI Oncology Program, in a press release. “This approval of pembrolizumab plus chemotherapy offers patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction cancer a new immunotherapy regimen that has demonstrated the potential to help these patients live longer.”

The press release noted that immune-mediated adverse reactions could be severe or fatal, impacting any organ system, tissue, and more than 1 body system simultaneously. Some of the immune-mediated reactions in the trial included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation.

“At Merck, we have a comprehensive development program across a broad range of gastrointestinal cancers with the goal of providing meaningful new options to patients and their healthcare providers,” said Marjorie Green, MD., senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a press release. “This latest approval of a KEYTRUDA-based treatment option is an important milestone for patients with advanced HER2-negative gastric or GEJ adenocarcinoma and reinforces Merck’s commitment to addressing the needs of these patients in the U.S.”


FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy as First-Line Treatment for Locally Advanced Unresectable or Metastatic HER2-Negative Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. Merck. News release. November 16, 2023. Accessed November 17, 2023. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-chemotherapy-as-first-line-treatment-for-locally-advanced-unresectable-or-metastatic-her2-negative-gastric-or-gastroesophageal-junction/

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