Immunotherapy for Gastric Cancer

First-Line Treatment Options

The American Society of Clinical Oncology and the European Society for Medical Oncology recommend nivolumab combined with chemotherapy as the preferred first-line immunotherapy for patients with PD-L1 CPS ≥5, while pembrolizumab is recommended for second-line treatment in MSI-H/dMMR tumors 1, 2
For patients with PD-L1 CPS ≥5, nivolumab plus fluoropyrimidine- and platinum-based chemotherapy is the standard first-line treatment, demonstrating significant improvements in overall survival (HR 0.71; 98.4% CI 0.59-0.86; P < 0.0001) and progression-free survival (HR 0.68; 98% CI 0.56-0.81; P < 0.0001) compared to chemotherapy alone 2, 3, 4
The ESMO guidelines assign this regimen a Level I, A recommendation with an ESMO-MCBS score of 4 3

Pembrolizumab is the standard second-line treatment for MSI-H/dMMR gastric cancer, with a Level II, A recommendation and ESMO-MCBS score of 3 2, 3
Dostarlimab-gxly is an alternative anti-PD-1 option for MSI-H/dMMR tumors 1
Nivolumab monotherapy is approved in Japan as third-line or later treatment regardless of PD-L1 status, based on the ATTRACTION-02 study showing superior OS 1

Before initiating immunotherapy, the following biomarkers must be tested: PD-L1 CPS score, HER2 status (IHC and FISH), and MSI-H/dMMR status 1, 2, 4, 5
The combined positive score (CPS) is preferred over tumor proportion score (TPS) for gastric cancer, as it includes PD-L1-positive lymphocytes and macrophages 4

The preferred chemotherapy regimen with immunotherapy is fluoropyrimidine plus platinum, with oxaliplatin preferred over cisplatin for tolerability 2, 3, 5
Acceptable fluoropyrimidines include 5-FU, capecitabine, or S-1 (in Asian populations) 2, 3

Pembrolizumab monotherapy should not be used as first-line treatment in unselected gastric cancer patients, as it showed lower response rates and inferior PFS compared to chemotherapy 2, 7
PD-L1 testing methodology matters, with CPS scoring preferred over TPS for gastric cancer 4
Trastuzumab should not be continued beyond first-line in HER2-positive gastric cancer, although trastuzumab deruxtecan may be considered in second-line 2, 3