Safety Profile of Nivolumab for Advanced Refractory Esophageal and Gastro-Esophageal Junction Cancer: Systemic Review and Meta-Analysis

Introduction: Recently Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1, was studied as adjuvant treatment for patients with advanced esophageal or gastro-esophageal junction (GEJ) cancer while taking or after taking standard therapy, chemoradiotherapy or surgery. Our study aimed to evaluate the safety profile of Nivolumab for advanced refractory esophageal or GEJ cancer. Methods: MEDLINE, the Cochrane Library, and EMBASE were searched up to 6/1/2021. The following keywords were used either alone or in combination: Nivolumab, esophageal cancer, esophagus cancer. Clinical trials that utilized Nivolumab for refractory esophageal cancer were included. The primary outcome was adverse effects from nivolumab, according to Common Terminology Criteria for Adverse Events v4.0. The rate of each event was calculated through meta-analysis. Data were analyzed with STATA version 16.0 (Stata Corp, College Station, TX, USA). Results: A total of 264 manuscripts were identified and 4 clinical studies including 966 patients met inclusion criteria. Patient median ages were more than 60 in all 4 studies and 727 (83.9%) were male. As the most common gastrointestinal side effect, the diarrhea rate was 18% (95% confidence interval (CI) 16-21%). The hepatic function abnormal rate was 12% (95% CI 10-15%). The nausea and constipation rate were 10% (95% CI 6-12%) and 17% (95% CI 13-22%). The decreased appetite rate was 13% (95% CI 11-16%). The rash rate was 15% (95% CI 13-17%). The pruritus rate was 11% (95% CI 9-13%). 10% (91% Cl 8-12%) patients discontinued due to adverse effects. Conclusion: In our meta-analysis, the incidence of side effects from nivolumab was similar to that seen in other types of solid tumor, which indicated tolerability and feasibility of treatment. However, more studies are warranted to validate the safety profile of nivolumab.Figure 1.: Adverse effect of nivolumab in patients with advanced refractory esophageal or GEJ cancer.