The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis

Abstract

ObjectiveThis systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC).BackgroundSeveral studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking.MethodsStudies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0.ResultsThirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26–0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31–0.65; nICT: 0.29, 95% CI: 0.26–0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1–2 and 3–4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56–0.84) and 0.16 (95% CI: 0.09–0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3–4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17–0.77; nICT: 0.14, 95% CI: 0.07–0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15–0.53; cisplatin: 0.04, 95% CI: 0.01–0.09; p<0.01).ConclusionNeoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.

Neoadjuvant Arterial Infusion Chemotherapy Combined With Immunotherapy in Treating Locally Advanced Lower Esophageal /Esophagogastric Junction Cancer

“…The neo-AICIT for locally advanced esophagus cancer is one of the most popular subjects in esophageal surgery. Relevant studies have shown that neo-AICIT may be superior to traditional neoadjuvant concurrent chemoradiotherapy, while the neoadjuvant concurrent chemoradiotherapy combined with immunotherapy may obtain a better effect that the neo-AICIT [23][24][25][26][27] . Although almost all studies have shown that the addition of immunotherapy on the basis of neoadjuvant chemotherapy or chemoradiotherapy does not signi cantly increase the side effects of drugs, the incidence of TRAEs and serious adverse events (SAEs) reached 71.95%-91.6% and 16.95%-19.4%, respectively [22][23][24][25][26] .…”

Neoadjuvant camrelizumab and chemotherapy in patients with resectable esophageal squamous cell carcinoma: A prospective, single-arm, open-label study

“…13 In previous studies, the majority of neoadjuvant PD-1 antibody-combined therapy involved 2 cycles, while 4 cycles of neoadjuvant PD-1 antibody-combined therapy are rarely used. 14 Lv et al reported that 3-4 cycles of neoadjuvant sintilimab, an immune checkpoint inhibitor targeting PD-1, plus chemotherapy in resectable locally advanced ESCC have a higher pathological complete response (pCR) rate than only 2 cycles of neoadjuvant sintilimab plus chemotherapy (47.9% compared to 12.5%; p = 0.0003). 15 This suggests that extending the neoadjuvant therapy cycle may increase the pCR rate, which is associated with prolonged overall survival (OS).…”