Efficacy and Safety of Neoadjuvant Immunotherapy Combined with Chemoradiotherapy vs. Combined with Chemotherapy in Esophageal Cancer: A Systematic Review and Meta-Analysis

Purpose/Objective(s)

Immunotherapy has showed promising clinical benefit in esophageal cancer. Both the neoadjuvant immunochemoradiotherapy (NICRT) and neoadjuvant immunochemotherapy (NICT) are making great progress. This meta-analysis was to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy versus combined with chemotherapy by synthesizing various trials.

Materials/Methods

A search of PubMed, Embase and Cochrane, in addition of major conferences, for clinical trials including single-arm trials, was conducted up to 30 August 2021. Efficacy was assessed by pathological complete response (pCR), major complete response (MPR) and R0 resection rate. Safety was evaluated by the incidence of ≥ grade 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Difference between NICRT and NICT groups was tested by Chi-square.

Results

A total of 20 studies was included, including 5 with NICRT and 15 with NICT. The overall pooled pCR, MPR, and R0 resection rate was 32%, 55%, and 96%, respectively. The pCR and R0 resection rates in NICRT vs NICT were 41% vs 30% (p=0.16) and 96% vs 96% (p=0.75), respectively. Only 1 trial in NICRT group reported a MPR of 89%, while the pooled MPR in NICT was 54%. Incidence of ≥ grade 3 TRAEs in NICRT vs NICT was 52% vs 20% (p=0.03), with high heterogeneity in both groups (I²=62%, p=0.10 vs I²=83%, p<0.01). Besides, the overall pooled rates of neoadjuvant therapy completion and surgical resection were 91% and 87%, respectively, which were proved not statistically different between the NICRT vs NICT group.

Conclusion

Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe. NICRT may not achieve better efficacy than NICT, but with potential increase of toxicity. Large trials are needed to confirm whether NICRT or NICT is more suitable for resectable esophageal cancer.