PD-1/PD-L1 Inhibitors Increase Pathological Complete Response in Locally Advanced Gastric Cancer: A Meta-analysis and Trial Sequential Analysis

Abstract

Background and objective: Gastric cancer (GC) remains a leading cause of morbidity and mortality worldwide. The current standard of care involves neoadjuvant chemotherapy (NACT) followed by radical gastrectomy. This study aims to evaluate the efficacy of neoadjuvant therapy with PD-1/PD-L1 inhibitors in comparison to chemotherapy alone for patients with locally advanced gastric cancer (LAGC).

Methods: We conducted a systematic search of PubMed, Web of Science, and Embase to identify studies examining the addition of PD-1/PD-L1 inhibitors to neoadjuvant therapy for LAGC. Odds ratios (OR) were calculated for binary outcomes, such as pathological complete response (pCR), with corresponding 95% confidence intervals (CI).

Results: Seven studies were included, encompassing a total of 1772 patients. Baseline median age ranged from 31 to 75 years. Most patients had an ECOG performance status score of 0 (942 patients), while 294 had an ECOG score of 1. The estimated pCR (OR 5.94, 95% CI 3.98-8.87; p < 0.000001) significantly favored the PD-1/PD-L1 inhibitors combined with chemotherapy over chemotherapy alone. Additionally, the incidence of certain adverse events increased significantly in the intervention group, including any-grade hypothyroidism (OR 4.55, 95% CI 2.27-9.10; p = 0.000019) and rash (OR 1.74, 95% CI 1.10-2.76; p = 0.017). Conversely, the control group showed a statistically significant lower incidence of grade ≥ 3 fatigue (OR 2.80, 95% CI 1.15-6.85; p = 0.024) compared to the intervention group.

Conclusion: This systematic review and meta-analysis indicate that the addition of PD-1/PD-L1 inhibitors to neoadjuvant chemotherapy is associated with a higher pathological complete response rate compared to chemotherapy alone in patients with locally advanced gastric cancer.

Keywords: Advanced gastric cancer; Anti-PD-1/PD-L1; Meta-analysis; Neoadjuvant.