FLOT Protocol Improves Esophageal Cancer Outcomes

TOPLINE: 

Perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) demonstrates superior outcomes than preoperative chemoradiotherapy in resectable esophageal adenocarcinoma, with overall survival at 3 years reaching 57.4% vs 50.7%. The median overall survival extends to 66 months with FLOT vs 37 months with preoperative chemoradiotherapy.

METHODOLOGY:

• Two multimodal approaches — preoperative chemoradiotherapy plus surgery and FLOT plus surgery — have demonstrated improved survival outcomes in patients with resectable esophageal adenocarcinoma.
• Previous trials established both preoperative chemoradiotherapy and FLOT as standards of care for treating nonmetastatic, resectable esophageal and esophagogastric junction adenocarcinoma.
• A phase 3, multicenter, randomized trial enrolled 438 patients with resectable esophageal adenocarcinoma from 25 centers in Germany between February 2016 and April 2020.
• Participants were randomly assigned in a 1:1 ratio to receive either FLOT (2600 mg/m² fluorouracil, 200 mg/m² leucovorin, 85 mg/m² oxaliplatin, and 50 mg/m² docetaxel) or preoperative chemoradiotherapy (2 mg/mL/min of carboplatin area under the curve and 50 mg/m² of paclitaxel weekly with 41.4 Gy of radiotherapy).
• The primary endpoint was overall survival, with a median follow-up duration of 55 months.

TAKEAWAY:

• Overall survival at 3 years was significantly higher in the FLOT group at 57.4% (95% CI, 50.1-64.0) vs 50.7% (95% CI, 43.5-57.5) in the preoperative chemoradiotherapy group (hazard ratio [HR], 0.70; 95% CI, 0.53-0.92; P = .01).
• Progression-free survival at 3 years was notably better in the FLOT group at 51.6% (95% CI, 44.3-58.4) vs 35.0% (95% CI, 28.4-41.7) in the preoperative chemoradiotherapy group (HR, 0.66; 95% CI, 0.51-0.85).
• Pathologic complete response rates were higher in the FLOT group at 16.7% than in the preoperative chemoradiotherapy group at 10.1%.
• Grade 3 or higher adverse events occurred in 58.0% of patients in the FLOT group and 50.0% of those in the preoperative chemoradiotherapy group, with mortality at 90 days after surgery at 3.1% and 5.6%, respectively.

IN PRACTICE:

“The current trial showed that overall survival was better with FLOT than with preoperative chemoradiotherapy among patients with resectable esophageal adenocarcinoma, including those with a clinical lymph-node stage of cN+ and those with a clinical tumor stage of cT3 or cT4, who made up most of the trial population,” the authors of the study wrote.

SOURCE:

This study was led by Jens Hoeppner, MD, University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, University of Bielefeld, Detmold, Germany. It was published online on January 23 in The New England Journal of Medicine.

LIMITATIONS:

According to the authors, while the trial was conducted in only one country, the epidemiology, quality of care, and treatment outcomes in Germany are largely reflective of those in high-income countries, where the incidence of esophageal adenocarcinoma is increasing.

DISCLOSURES:

This study received funding support from the German Research Foundation.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.