Gastric cancer is the fifth most common malignant tumor worldwide and the third leading cause of cancer-related deaths. Most patients are diagnosed at an advanced stage with a very poor prognosis. For resectable locally advanced gastric cancer (LAGC), neoadjuvant chemotherapy (NAC) is recommended. However, treatment regimens recommended in different guidelines vary significantly. Recently, a team from The Sixth Affiliated Hospital of Sun Yat-sen University conducted a retrospective study to evaluate the efficacy of triple-agent versus dual-agent neoadjuvant (NAC) therapy for patients with locally advanced gastric cancer (LAGC). The results were published in the journal BMC Cancer.

This paper reviewed 227 patients with locally advanced gastric cancer (LAGC) who received neoadjuvant chemotherapy (NAC) followed by radical gastrectomy. Using propensity score matching (PSM), 140 patients with similar baseline characteristics were selected. Of these, 70 cases were treated with a dual-drug regimen containing platinum and fluorouracil, while the other 70 received a triple-drug regimen consisting of docetaxel, platinum, and fluorouracil.

FLOT and SOX are the most commonly used regimens in the study, accounting for 90%. Other regimens included FOLFOX, CAPOX, and DCF, all of which are clinically common regimens. All patients received an average of 4 cycles of NAC before surgery. Before and after PSM, the incidence of neutropenia and anemia was higher in the triple-drug treatment group, while thrombocytopenia was more common in the dual-drug group. There was no significant difference in the incidence of grade 3/4 hematologic toxicity.

There was no significant difference in the R0 resection rate between the two groups (dual-drug group: 90.1%, 82/91; triple-drug group: 88.2%, 120/136, p = 0.829). After PSM matching, the R0 resection rates were similar in both the dual-drug and triple-drug groups (both 88.6%, 62/70, p = 0.1). The incidence of complications (Clavien-Dindo 2 - 4 grade) was significantly higher in the triple-drug group than in the control group (before PSM: dual-drug 8.8%, 8/91 vs. triple-drug 27.2%, 37/136, p = 0.001; after PSM: dual-drug 5.7%, 4/70 vs. triple-drug 27.1%, 19/70, p = 0.001), particularly surgical-related abdominal infections, mainly caused by anastomotic leaks. Regarding pathological results, the two cohorts showed statistically similar TRG values before and after PSM analysis. The triple-drug treatment had a higher rate of pathological complete response (0 grade: before PSM, dual-drug 11.0%, 10/91; triple-drug 16.2%, 22/136, p = 0.686; after PSM, dual-drug 11.4%, 8/70; triple-drug 15.7%, 11/70, p = 0.642), but the difference was not statistically significant.

The median follow-up time was 31 months. Before PSM, the triple-drug group had a shorter disease-free survival (DFS), but the difference was not significant after PSM (1-year DFS rate, dual-drug 77.1% vs. triple-drug 68.6%, p = 0.178). The overall survival (OS) of the two groups was similar before and after PSM (3-year OS rate after PSM, dual-drug 54.3% vs. triple-drug 60.9%, p = 0.941).

In the subgroup survival analysis, the triplet therapy cohort did not show any advantage in any subgroup. In patients with moderately differentiated adenocarcinoma, triplet NAC was even associated with shorter DFS. Therefore, these data suggest that, compared to dual-drug regimens, triplet regimens do not provide additional survival benefits.

Overall, the study indicates that, compared to dual-drug regimens, triplet neoadjuvant therapy regimens do not offer additional survival benefits. They may even lead to a higher risk of postoperative complications.