Home›Oncology› PD-1/PD-L1 inhibitor plus chemotherapy improves overall survival in advanced gastric and esophageal junction cancer
PD-1/PD-L1 inhibitor plus chemotherapy improves overall survival in advanced gastric and esophageal junction cancerPD-1 Inhibitors Plus Chemotherapy Improve Survival in Gastric Cancer
Frontiers in MedicinePublished September 10, 2026DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Consider PD-1/PD-L1 inhibitor plus chemotherapy for first-line advanced gastric cancer to improve survival despite higher toxicity.
This meta-analysis evaluated the efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy compared to chemotherapy alone or placebo plus chemotherapy in 6,517 adults with previously untreated unresectable, recurrent, locally advanced, or metastatic gastric or gastroesophageal junction cancer.
The analysis found that the addition of PD-1/PD-L1 inhibitors significantly improved overall survival (HR, 0.79; 95% CI, 0.75-0.85) and progression-free survival (HR, 0.78). The objective response rate increased (RR, 1.24; 95% CI, 1.18-1.31). Notably, the progression-free survival effect was more pronounced in Asian-only or China-only trials (HR, 0.66) compared to the global cohort (HR, 0.78).
Safety data indicated that the combination therapy was associated with higher rates of grade 3 or higher treatment-related adverse events (RR, 1.15; 95% CI, 1.08-1.23), serious treatment-related adverse events (RR, 1.53; 95% CI, 1.29-1.83), and treatment discontinuation (RR, 1.53; 95% CI, 1.37-1.72). The authors noted that the estimate for treatment-related death was statistically inconclusive due to a wide confidence interval (RR, 1.54; 95% CI, 0.75-3.16).
Clinically, the combination provides a consistent survival and response benefit in first-line treatment for advanced gastroesophageal junction or gastric cancer. However, clinicians should weigh these benefits against increased clinically relevant toxicity and higher rates of treatment discontinuation.
How this fits prior evidence
This meta-analysis addresses the management of advanced gastric cancer, a condition where other interventions have shown specific benefits. It complements findings that perioperative immune checkpoint inhibitors with chemotherapy increase pCR in resectable gastric cancer. It also provides a broader look at systemic options for advanced disease compared to the reported durable remission in a single case of metastatic gastric cancer using disitamab vedotin and camrelizumab.
A large analysis of 6,517 adults with advanced gastric or gastroesophageal junction cancer looked at the effects of combining PD-1 or PD-L1 inhibitors with chemotherapy. The study compared this combination to chemotherapy alone or a placebo with chemotherapy. The results showed that patients receiving the combination therapy had significantly better overall survival and higher response rates compared to those receiving only chemotherapy.
While the treatment showed clear benefits in survival and progression-free survival, it also came with higher risks. The data showed an increase in serious treatment-related events and a higher rate of treatment discontinuation. One specific measure regarding treatment-related death was not statistically certain due to a wide range of data.
This finding suggests that while the combination therapy is more effective at managing advanced cancer, it also carries more side effects. Because every patient's health is different, patients should talk to their doctors to weigh these survival benefits against the potential for increased toxicity.
What this means for you:
Combining PD-1 or PD-L1 inhibitors with chemotherapy improves survival in advanced gastric cancer but increases risk.
Common questions
What are the benefits of adding PD-1 inhibitors to chemotherapy?
Adding PD-1 or PD-L1 inhibitors to chemotherapy significantly improved overall survival and progression-free survival for patients with advanced gastric or gastroesophageal junction cancer. The study also showed an increased objective response rate, meaning more patients saw a measurable reduction in their tumors.
Are there side effects to this combination treatment?
Yes, the combination treatment was associated with a higher risk of serious treatment-related adverse events and a higher rate of treatment discontinuation. While it improved survival, the increased risk of these complications means the treatment has higher toxicity than chemotherapy alone.
Who is this treatment intended for?
This treatment was studied in adults with previously untreated, unresectable, recurrent, locally advanced, or metastatic gastric or gastroesophageal junction cancer. It is intended for patients who need more intensive options than standard chemotherapy alone.
BackgroundFirst-line chemoimmunotherapy has become a major therapeutic strategy for advanced gastric and gastroesophageal junction cancer, yet the magnitude of survival benefit, regional consistency, and toxicity trade-offs remain important considerations. We conducted an systematic review and meta-analysis of randomized controlled trials evaluating PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone or placebo plus chemotherapy.MethodsPubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov were searched from inception to March 1, 2026. Eligible studies enrolled adults with previously untreated unresectable, recurrent, locally advanced, or metastatic gastric or gastroesophageal junction cancer. Hazard ratios were pooled for overall survival and progression-free survival, and risk ratios were pooled for objective response rate and safety outcomes using random-effects models. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE.ResultsSeven randomized controlled trials including 6,517 patients were analyzed. PD-1/PD-L1 inhibitor plus chemotherapy significantly improved overall survival and progression-free survival. Objective response rate was also increased (RR, 1.24; 95% CI, 1.18–1.31), with negligible observed heterogeneity (I² = 0.0%). Overall survival effects were similar in global trials (HR, 0.79; 95% CI, 0.75–0.85) and Asian-only or China-only trials (HR, 0.81; 95% CI, 0.73–0.91; P for subgroup difference = 0.70). The progression-free survival effect was greater in Asian-only or China-only trials (HR, 0.66 vs. 0.78; P for subgroup difference = 0.02), although this analysis was exploratory. Combination therapy increased grade ≥3 treatment-related adverse events (RR, 1.15; 95% CI, 1.08–1.23), serious treatment-related adverse events (RR, 1.53; 95% CI, 1.29–1.83), and treatment discontinuation (RR, 1.53; 95% CI, 1.37–1.72). The pooled estimate for treatment-related death was statistically inconclusive (RR, 1.54; 95% CI, 0.75–3.16); the wide confidence interval indicated substantial imprecision and could not exclude clinically important increases or decreases in treatment-related mortality.ConclusionsFirst-line PD-1/PD-L1 inhibitor + chemotherapy provides a consistent survival and response benefit in advanced gastroesophageal junction or gastric cancer, but with increased clinically relevant toxicity. These findings support chemoimmunotherapy as a preferred first-line strategy for appropriately selected patients, with treatment decisions guided by biomarker status, patient fitness, and toxicity risk.
