Pembrolizumab Plus Trastuzumab and Chemotherapy for HER2-Positive Gastric or Gastro-oesophageal Junction Adenocarcinoma

Abstract

he combination of pembrolizumab, and trastuzumab chemotherapy has long been investigated in the treatment of HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. HER2-positive gastric or gastroesophageal junction adenocarcinoma refers to cancers that overexpress the human epidermal growth factor receptor 2 (HER2), which is associated with more aggressive tumor behavior. Pembrolizumab is a monoclonal antibody that targets the programmed cell death protein 1 (PD-1) receptor, a checkpoint protein on immune cells. By blocking PD-1, pembrolizumab helps unleash the immune system to target and attack cancer cells. Trastuzumab is another monoclonal antibody that specifically targets HER2-positive cancer cells. It has been a standard treatment for HER2-positive breast cancer and has been explored in HER2-positive gastric and gastroesophageal junction cancers. Janjigian and colleagues revealed the interim analysis of a randomized, phase 3 KEYNOTE-811 trial which involved 168 medical centers in 20 countries worldwide. They found that compared with placebo, pembrolizumab significantly improved progression-free survival when combined with first-line trastuzumab and chemotherapy for metastatic HER2-positive gastro-oesophageal cancer, specifically in patients with tumors with a PD-L1 combined positive score of 1 or more. They stated that the overall survival follow-up is ongoing and will be reported at the final analysis.  Lancet. 2023 Dec 9;402(10418):2197-2208. doi: 10.1016/S0140-6736(23)02033-0.