Neoadjuvant therapy with immune checkpoint inhibitors in combination with chemotherapy vs. chemotherapy alone in HER2(-) locally advanced gastric cancer: A propensity score-matched cohort study

Background: This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapyvs. chemotherapy, and neoadjuvant tripletvs. doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC).Methods: We included LAGC patients from 47 hospitals in China’s National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapyvs. chemotherapy alone, and neoadjuvant tripletvs. doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS).Results: A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13%vs. 7.61%, χ2 = 4.039,P = 0.044), and the 2-year (77.60%vs. 61.02%, HR = 0.67, 95% confidence interval [CI] 0.43-0.98,P = 0.048) and 3-year (70.55%vs. 61.02%, HR = 0.58, 95% CI 0.32-0.93,P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons.Conclusions: Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.