Combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.MethodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).ResultsA total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%–25.5%] and 44.0% (95% CI, 34.1%–53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%–94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%–66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%–99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].ConclusionThis systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.

Safety and efficacy of minimally invasive gastrectomy for older patients with gastric cancer after neoadjuvant chemotherapy and immunotherapy: a propensity score-matched analysis

“…Our study revealed that 13 (21.3%) and 27 (44.2%) older patients with GC in the NICT-MIG group achieved pCR and MPR, respectively. These findings indicate a comparable tumor response in older patients, aligning with previous studies conducted across all age populations [ 22 ]. We also found the comparable 2-year OS and RFS between two groups, especially for pTNM satege I patients undergoing upfront MIG and ypTNM stage 0-I patients who had better tumor response in the NICT-MIG group.…”

Development and validation of a nomogram to predict pathological complete response in patients with locally advanced gastric adenocarcinoma treated with neoadjuvant chemotherapy in combination with PD-1 antibodies

“…The limitations in the efficacy of current immunotherapies, mainly involving immune checkpoint inhibitors, have emphasized the need to enhance our comprehension of combination therapeutic strategies for improving outcomes among patients who exhibit poor response to single-agent immunotherapy ( 27 ). To further enhance the efficacy of neoadjuvant therapy in patients with advanced gastric adenocarcinoma, multimodal treatment regimens incorporating neoadjuvant chemotherapy and PD-1 antibody immunotherapy prior to surgical resection are being increasingly employed ( 28 ). However, the choice of population for neoadjuvant chemotherapy in combination with PD-1 antibody therapy remains controversial.…”

Targeting CD74-positive macrophages improves neoadjuvant therapy in cervical cancer as revealed by single-cell transcriptomics analysis

“…In the treatment process of many tumors, including gastric and ovarian cancer, general perspectives indicated that the combination of chemotherapy and immunotherapy can synergistically improve the effect of anti-cancer. This might be due to the reduced immune suppression of TME with the combination of chemotherapeutics and the enhanced elimination and recognition of tumors by the immune system 10,11 . PD-L1 blockade in combination with chemotherapy has already been applied in combination with chemotherapy in several clinical trials.…”