Comparison of efficacy and safety between neoadjuvant chemotherapy and neoadjuvant immune checkpoint inhibitors combined with chemotherapy for locally advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis

Abstract

Background: The application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy (NICT) in treating locally advanced oesophageal squamous cell carcinoma (ESCC) is a subject of considerable research interest. In light of this, we undertook a comprehensive meta-analysis aiming to compare the efficacy and safety of this novel approach with conventional neoadjuvant chemotherapy (NCT) in the management of ESCC.

Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to gather relevant literature on the efficacy and safety of NICT compared to conventional NCT in locally advanced ESCC published before June 2023. Effect indicators, including odds ratios (ORs) with associated 95% CIs, were employed to evaluate the safety and efficacy outcomes. The risk of bias was assessed using the Cochrane bias risk assessment tool, and s ubgroup analysis and sensitivity analysis were conducted to investigate the findings further.

Results: A total of nine studies qualified for the meta-analysis, all of which investigated the efficacy and safety of NICT compared to conventional NCT. The pooled rates of pathologic complete response and major pathologic response in the NICT group were significantly higher compared to the NCT group, with values of 26.9% versus 8.3% ( P <0.00001) and 48.1% versus 24.6% ( P <0.00001), respectively. The ORs for achieving pathologic complete response and major pathologic response were 4.24 (95% CI, 2.84-6.32, I 2 =14%) and 3.30 (95% CI, 2.31-4.71, I 2 =0%), respectively, indicating a significant advantage for the NICT group. Regarding safety outcomes, the pooled incidences of treatment-related adverse events and serious adverse events in the NICT group were 64.4% and 11.5%, respectively, compared to 73.8% and 9.3% in the NCT group. However, there were no significant differences observed between the two groups in terms of treatment-related adverse events (OR=0.67, 95% CI, 0.29-1.54, P =0.35, I 2 =58%) or serious adverse events (OR=1.28, 95% CI, 0.69-2.36, P =0.43, I 2 =0%). Furthermore, no significant differences were found between the NICT and NCT groups regarding R0 resection rates, anastomotic leakage, pulmonary infection, and postoperative hoarseness.

Conclusions: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrate efficacy and safety in treating resectable oesophageal squamous cell carcinoma. Nevertheless, additional randomized trials are required to confirm the optimal treatment regimen.

Figure 1

Flow chart of literature search and study selection.

Figure 2

The risk of bias of the included studies. (A) Risk of bias of non-randomized trials; (B) Risk of bias of randomized trials.

Figure 3

Forest plot of the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy and neoadjuvant chemotherapy. (A) pCR rate; (B) MPR rate; (C) incidence of SAEs; (D) incidence of TRAEs; (E) R0 resection rate; (F) incidence of anastomotic leakage; (G) incidence of pulmonary infection; (H) incidence of postoperative hoarseness. MPR, major pathological response; NICT, neoadjuvant immune checkpoint inhibitors combined with chemotherapy; NCT, neoadjuvant chemotherapy; pCR, complete pathological response; SAE, severe adverse event; TRAE, treatment-related adverse event.

Figure 4

Sensitivity analysis.(A) pCR rate;(B) MPR rate; (C) incidence of SAEs; (D) incidence of TRAEs; (E) R0 resection rate; (F) incidence of anastomotic leakage;(G) incidence of pulmonary infection; (H) incidence of postoperative hoarseness. MPR, major pathological response; pCR, complete pathological response; SAE, severe adverse event; TRAE, treatment-related adverse event.

Figure 5

Publication bias of included studies was conducted based on Egger regression tests for (A) pCR rate; (B) MPR rate; (C) incidence of SAEs; (D) incidence of TRAEs; (E) R0 resection rate; (F) incidence of anastomotic leakage; (G) incidence of pulmonary infection; (H) incidence of postoperative hoarseness. MPR, major pathological response; pCR, complete pathological response; SAE, severe adverse event; TRAE, treatment-related adverse event.

Figure 6

Publication bias of included studies was conducted based on funnel plot for (A) pCR rate; (B) MPR rate; (C) incidence of SAEs; (D) incidence of TRAEs; (E) R0 resection rate; (F) incidence of anastomotic leakage; (G) incidence of pulmonary infection; (H) incidence of postoperative hoarseness. MPR, major pathological response; pCR, complete pathological response; SAE, severe adverse event; TRAE, treatment-related adverse event.

Figure 7

Forest plot of the efficacy and safety of subgroup analysis based on study type. (A) pCR rate; (B) MPR rate; (C) incidence of SAEs; (D) incidence of TRAEs; (E) R0 resection rate; (F) incidence of anastomotic leakage; (G) incidence of pulmonary infection. MPR, major pathological response; pCR, complete pathological response; SAE, severe adverse event; TRAE, treatment-related adverse event.

Figure 8

Forest plot of the efficacy and safety of subgroup analysis based on chemotherapy regimen. (A) pCR rate; (B) incidence of TRAEs; (C) R0 resection rate; (D) incidence of anastomotic leakage; (E) incidence of pulmonary infection. DP, Docetaxel in combination with platinum; pCR, complete pathological response; RAE, treatment-related adverse event; TP, Taxol in combination with platinum.

Figure 9

Forest plot of the efficacy and safety of subgroup analysis based on neoadjuvant treatment cycles. (A) pCR rate; (B) incidence of TRAEs; (C) R0 resection rate; (D) incidence of anastomotic leakage; (E) incidence of pulmonary infection. pCR, complete pathological response; RAE, treatment-related adverse event; TRAE, treatment-related adverse event.