Asian patients respond better to immunotherapy for advanced HER2-negative gastric cancer

Patients with advanced HER2-negative gastric cancer respond differently to immunotherapy based on whether they are Asian or non-Asian, with Asian patients often seeing better outcomes likely due to a mix of biological, environmental and clinical differences, according to a study published in February 2026 in Cancer Biology and Medicine.

Immunotherapy has become a standard treatment for advanced HER2-negative gastric cancer, often given with chemotherapy as the first treatment.

Gastric cancer is the fifth most diagnosed cancer worldwide, with roughly 1 million new cases diagnosed in 2018, and the third most common cause of cancer-related deaths.

Research shows that outcomes can differ by region, with Asian patients often having higher response rates and longer survival. These differences may come from biological factors, such as age at diagnosis, tumor genetics and immune system differences. Environmental factors, including diet, Helicobacter pylori infection and gut microbiome, could also affect how patients respond.

Understanding these differences calls for more diverse clinical trials and personalized treatments for all patients.

Researchers from the Fifth Medical Center at the Chinese General Hospital in Beijing and the country’s MSD Value & Implementation Group examined why immunotherapy responses differ between Asian and non-Asian patients with advanced HER2-negative gastric cancer. Researchers analyzed results from phase 2 and 3 clinical trials, meta-analyses and large observational datasets all published between 2019 and 2024. They compared outcomes such as overall survival, progression-free survival and response rates across populations descending from East Asian groups and primarily white and western populations (U.S., Canada, Europe).

The review also looked at epidemiologic data, including age, sex and stage at diagnosis. In addition, the authors examined molecular and genetic findings, such as somatic mutations and tumor subtypes, using data from sources including The Cancer Genome Atlas and other relating studies.

Immune system features, including tumor microenvironment and PD-L1 expression, were reviewed. Environmental and lifestyle factors, such as Helicobacter pylori infection, diet and gut microbiome composition, were also examined. Together, these data were combined and reviewed to identify patterns and potential drivers of differences in immunotherapy outcomes across populations.

Results showed that in first-line studies combining immune checkpoint inhibitors with chemotherapy, objective response rates ranged from about 22.6% to 66.0% in Asian patients compared with 14.5% to 60.0% overall. Median progression-free survival was also slightly longer in Asian groups, ranging from 4.1 to 8.5 months, while overall survival reached 10.5 to 22.7 months. Meta-analyses confirmed this trend, showing stronger survival benefits for Asian patients, although both groups benefited from treatment.

Safety outcomes were similar across populations, with serious adverse events reported in about 10% to 20% of patients. Researchers also found key biological and clinical differences that may help explain these results. Asian patients were often younger at diagnosis and more likely to have tumor types linked to better immune response.

Differences in gene mutations, tumor biology, and molecular subtypes were also observed. In addition, factors such as higher rates of Helicobacter pylori infection, diet and gut microbiome patterns were found to influence immune activity and treatment response; however, findings remain mixed and need further study.

This review has several strengths, including a broad look at many possible reasons for differences in immunotherapy response, such as genetics, tumor biology, immune factors and the gut microbiome. It brings together data from clinical trials and lab studies to provide a more complete picture.

However, there are limitations. For example, many of the findings come from small samples, and some data may not apply to all patient groups or to advanced disease. Results are also sometimes inconsistent across regions and studies.

The authors suggested future trials should include diverse patient groups and plan for ethnic comparisons. They also called for more research that combines genomic, immune and microbiome data to find better biomarkers and guide more personalized treatment.