S996 Evaluating the Safety and Efficacy of FLOT Regimen in the Treatment of Esophageal Cancer: A Systematic Review and Meta-Analysis

Introduction: Esophageal cancer (EC) is the sixth most common cancer worldwide and the fifth most common in the U.S. Currently, the standard curative treatment of choice for advanced esophageal cancer includes chemotherapy and radiotherapy. However, the effectiveness of these treatments in achieving sustained tumor control and improving overall survival remains limited. Fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) regimen is a new promising treatment approach that offers a superior therapeutic advantage over the current treatment options utilizing the combination of 5-fluorouracil, platinum salts, and taxanes. Methods: We systematically searched PubMed, Embase, and Cochrane databases through May 5, 2025, to include all randomized controlled trials (RCTs) and observational studies for evaluating the efficacy of FLOT for the treatment of EC. The outcomes of interest in our meta-analysis were tumor resection rate, post-operative mortality and morbidity, and grade 3/4 adverse events. Data was extracted and analyzed on RevMan v.5.4.1. The random-effects model was used to calculate the weighted pooled risk ratio (RR) with the corresponding 95% confidence intervals (CI) of our desired outcome. The I2 and χ2 statistics assessed heterogeneity with a P-value of < 0.05, considered statistically significant. Results: Our search identified a total of 12 studies with 6,032 patients (3,009 intervention group; 3,023 control group). We found that the use of FLOT demonstrated statistically significant results in tumor resection rate (RR 1.07; 95% CI 1.02 to 1.12; I2 = 71%; P = 0.003), and postoperative mortality (RR 0.41; 95% CI 0.26 to 0.67; I2 = 0%; P = 0.0003). However, it is notable that postoperative morbidity (RR 1.00; 95% CI 0.83 to 1.22; I2 = 0%; P = 0.98); and grade 3/4 adverse events (RR 0.82; 95% CI 0.60 to 1.11; I2 = 0%; P = 0.20) showed no statistically significant benefit with the combination treatment. Conclusion: Our meta-analysis demonstrated that the FLOT regimen improves patient prognosis by enhancing tumor resection rate and reducing postoperative mortality in esophageal cancer. However, it also demonstrated that FLOT therapy showed no statistically significant benefit on post-operative morbidity, and grade 3/4 adverse events. Therefore, further large scale RCTs are needed to better understand the impact of FLOT therapy on esophageal cancer.