Highlights
- •Newly approved immune checkpoint inhibitors (ICI) enrich options for GEJ/GC therapies.
- •Relevant phase II/III trials focus on important biomarkers including PD-L1 assessment.
- •Next research may clarify ICI resistance mechanisms and varied gender responses.
Abstract
The new era of immunotherapy is successfully implemented in the treatment of metastatic/locally
advanced esophagogastric adenocarcinoma (EGAC), as it has been investigated in combinations
with/without chemotherapy in human epidermal growth factor receptor 2 (Her2)-positive
and Her2-negative tumors. Recent approvals of immune checkpoint inhibitors (ICI) enrich
the therapeutic landscape in nearly every therapeutic line. Based on CHECKMATE-649,
the combination of nivolumab and chemotherapy in first-line therapy of programmed
cell death protein 1 (PD-L1)-positive patients with advanced gastroesophageal junction
cancer (GEJC), esophageal cancer (EC), and gastric cancer (GC) was approved in Europe
for PD-L1 combined positivity score (CPS) ≥ 5 patients and independently from PD-L1
score in the USA and Asia. Based on KEYNOTE-590, patients with advanced GEJC and EC
qualify for the combination of pembrolizumab plus chemotherapy in Europe (CPS ≥ 10)
and the USA. For Her2-positive patients, trastuzumab with first-line chemotherapy
plus pembrolizumab has beneficial response rates and resulted in approval in the USA
(KEYNOTE-811). In third-line therapy, superior overall survival (OS) was achieved
by the administration of nivolumab (approval in Japan, ATTRACTION-02), and pembrolizumab
shows a positive effect on the duration of response (KEYNOTE-059). Questions of resistance
to immunotherapy or the role of gender in response to ICI need to be clarified. This
review provides an overview of the current approvals of ICI in advanced EGAC and reflects
results of relevant phase II/III trials with focus on possible biomarkers, including
PD-L1 CPS and microsatellite-instability (MSI) status.
Keywords
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Article info
Publication history
Published online: September 29, 2022
Accepted:
August 22,
2022
Received in revised form:
August 12,
2022
Received:
April 16,
2022
Identification
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