The optimal neoadjuvant chemotherapy regimen for locally advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and Bayesian network meta-analysis

Abstract

Background: Neoadjuvant chemotherapy (NAC) for locally advanced gastric and gastroesophageal junction adenocarcinoma (LAGC) has been recommended in several guidelines. However, there is no global consensus about the optimum of NAC regimens. We aimed to determine the optimal NAC regimen for LAGC.

Methods: A systematic review and Bayesian network meta-analysis was performed. The literature search was conducted from inception to June 2022. The odds ratio (OR) value and 95% confidence interval (95% CI) were used for assessment of R0 resection rate and pathological complete response rate (pCR) as primary outcomes. The hazard ratio (HR) value and 95% CI were interpreted for the assessment of overall survival (OS) and disease-free survival (DFS) as second outcomes. The risk ratio (RR) value and 95% CI were used for safety assessment.

Results: Twelve randomized controlled trials were identified with 3846 eligible participants. The network plots for R0 resectability, OS, and DFS constituted closed loops. The regimens of TPF (taxane and platinum plus fluoropyrimidine), ECF (epirubicin and cisplatin plus fluorouracil), and PF (platinum plus fluoropyrimidine) showed a meaningful improvement of R0 resectability, as well as OS and/or DFS, compared with surgery (including surgery-alone and surgery plus postoperative adjuvant chemotherapy). Importantly, among these regimens, TPF regimen showed significant superiority in R0 resection rate (versus ECF regimen), OS (versus ECF regimen), DFS (versus PF and ECF regimens), and pCR (versus PF regimen).

Conclusions: The taxane-based triplet regimen of TPF is likely the optimal neoadjuvant chemotherapy regimen for LAGC patients.

Keywords: Bayesian network meta-analysis; Gastric cancer; Gastroesophageal junction cancer; Neoadjuvant chemotherapy; Systematic review.

Fig. 1

Flowchart of literature retrieval

Fig. 2

Network meta-analysis of R0 resection rate. A Network of R0 resection rate. The size of the nodes and the thickness of the edges are weighted according to the number of studies evaluating each treatment and direct comparison, respectively. B Forest plots of comparisons for R0 resection rate (S, surgery). C Comparative effectiveness of neoadjuvant treatments in network meta-analysis. Hazard ratio (HR) (95% CI) for comparisons is in cells in common between column-defining and row-defining treatment. Bold cells are significant. HR < 1 favors column-defining treatment. D The SUCRA values of each regimen and surgery

Fig. 3

Network meta-analysis of OS and DFS. A Network of OS. The size of the nodes and the thickness of the edges are weighted according to the number of studies evaluating each treatment and direct comparison, respectively. B Forest plots of comparisons for OS (S, surgery). C Network of DFS. The size of the nodes and the thickness of the edges are weighted according to the number of studies evaluating each treatment and direct comparison, respectively. D Forest plots of comparisons for DFS (S, surgery). E Comparative effectiveness of neoadjuvant treatments in network meta-analysis. Hazard ratio (HR) (95% CI) for comparisons is in cells in common between column-defining and row-defining treatment. Bold cells are significant. For OS, HR  < 1 favors column-defining treatment. For DFS, HR  < 1 favors row-defining treatment

Fig. 4

The pCR rate of each regimen. A The pCR rate was 11.21% for TPF regimen, 7.21% for ECF regimen, 5.01% for PF regimen and 5.13% for TP regimen. B Forest plots of comparisons for pathological complete response rate