Abstract
BACKGROUD: The utilization of neoadjuvant therapy, encompassing chemotherapy, molecular targeted therapy, and immunotherapy, has demonstrated a significant enhancement in the radical resection rate and an improved prognosis for patients with locally advanced gastric cancer (LAGC). The purpose of this meta-analysis was to evaluate the efficacy and safety of neoadjuvant chemotherapy (NCT) in combination with targeted therapy or (and) immunotherapy for LAGC patients. METHODS: The PubMed, EmBase, and Cochrane Library databases were systematically searched to identify clinical studies comparing the efficacy of different neoadjuvant regimens in LAGC patients. Subsequently, paired and network meta-analyses were conducted using Stata software to evaluate the pooled results of different neoadjuvant regimens, including NCT, neoadjuvant immunotherapy plus chemotherapy (NICT), NCT plus targeted therapy (NCTT), and NICT plus targeted therapy (NICTT). RESULTS: 21 studies [six randomized controlled trials (RCTs) and 15 non-RCTs] fulfilled the inclusion criteria were incorporated into the meta-analysis. Pairwise meta-analysis revealed that the NICTT, NICT, and NCTT groups exhibited a higher incidence of pathological complete response (pCR), major pathological response (MPR), and R0 resection compared to the NCT group. Compared to the NCT group, both the NICTT and NCTT groups demonstrated a tendency towards experiencing more severe treatment-related adverse events (TRAEs), while the NICT and NCTT groups exhibited a lower 2-year recurrence rate. Additionally, network meta-analysis revealed that the NICTT group exhibited superior efficacy in achieving pCR, albeit being associated with a higher incidence of severe TRAEs. CONCLUSION: Compared to NCT alone, the combined application of targeted therapy and/or immunotherapy demonstrates greater efficacy in tumor downstaging and achieving pCR. However, it is crucial to remain vigilant regarding the occurrence of severe TRAEs. The future adoption of NICTT as a mainstream treatment is anticipated, however, further high-quality clinical studies are imperative to substantiate its efficacy.