Advanced gastric (stomach) cancer and cancer of the gastro-oesophageal junction (GOJ) have limited treatment options and historically poor outcomes. Pembrolizumab has demonstrated meaningful benefit across several settings in these cancers, and is now part of the standard first-line treatment approach for eligible patients.
KEYNOTE-859: First-line gastric and GOJ cancer
KEYNOTE-859 evaluated pembrolizumab in combination with fluoropyrimidine and platinum chemotherapy as first-line treatment for advanced HER2-negative gastric or GOJ cancer. In patients with CPS 1 or higher - which represents the majority of patients with these cancers - adding pembrolizumab to chemotherapy produced a significant improvement in overall survival compared to chemotherapy alone. The benefit was most pronounced in patients with higher CPS scores. KEYNOTE-859 established pembrolizumab as a standard first-line component for PD-L1-positive gastric and GOJ cancer.
KEYNOTE-811: HER2-positive gastric and GOJ cancer
Approximately 15-20% of gastric and GOJ cancers overexpress HER2 - a growth factor receptor targetable with the drug trastuzumab. KEYNOTE-811 evaluated adding pembrolizumab to trastuzumab plus chemotherapy in this HER2-positive population. Response rates were significantly higher with the three-drug combination, and progression-free survival was improved. Pembrolizumab is now approved in combination with trastuzumab and chemotherapy for HER2-positive gastric and GOJ cancer.
PD-L1 assessment in gastric cancer
The Combined Positive Score (CPS) is used in gastric and GOJ cancer. Testing is performed on tumour tissue from biopsy or surgical specimens. CPS thresholds vary by indication - CPS 1 is the relevant threshold for KEYNOTE-859, while higher scores are associated with greater benefit. HER2 status testing is also standard for newly diagnosed advanced disease, as it determines treatment eligibility for the trastuzumab-containing regimen.
Home administration considerations
Gastric cancer treatment in the first-line setting involves combination chemotherapy that requires hospital administration. Once the chemotherapy phase is complete, the pembrolizumab maintenance component can be given as a subcutaneous injection at home. For patients dealing with the nutritional and energy challenges that gastric cancer often brings, removing the ongoing hospital visit burden is a meaningful practical benefit.
Being treated for gastric or GOJ cancer?
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