A recent phase III trial, ESOPEC, published in The New England Journal of Medicine, has revealed that perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) significantly improves overall survival in patients with resectable esophageal adenocarcinoma compared to preoperative chemoradiotherapy.
The multicenter, open-label trial, led by Jens Hoeppner, MD, from Bielefeld University in Detmold, Germany, randomized 438 patients between February 2016 and April 2020. The FLOT arm (n = 221) received four 2-week cycles of FLOT before surgery and four cycles after surgery. The chemoradiotherapy arm received carboplatin (AUC = 2) and paclitaxel (50 mg/m²) weekly for five weeks, concurrent with external-beam radiotherapy at 41.4 Gy.
The primary endpoint was overall survival. After a median follow-up of 55 months, the 3-year overall survival rate was 57.4% (95% CI, 50.1%-64.0%) in the FLOT group compared to 50.7% (95% CI, 43.5%-57.5%) in the chemoradiotherapy group (HR = 0.70, 95% CI = 0.53-0.92, P = .01). The 5-year overall survival rates were 50.6% and 38.7%, respectively. Median overall survival was 66 months in the FLOT arm versus 37 months in the chemoradiotherapy arm.
Progression-Free Survival
Progression-free survival at 3 years was also significantly higher in the FLOT group at 51.6% (95% CI, 44.3%-58.4%) compared to 35.0% (95% CI, 28.4%-41.7%) in the chemoradiotherapy group (HR = 0.66, 95% CI = 0.51-0.85).
Adverse Events
Grade 3 or higher adverse events were more frequent in the FLOT group (58.0%) compared to the chemoradiotherapy group (50.0%). The most common adverse events in the FLOT group were neutropenia (19.8%), diarrhea (6.8%), leukopenia (6.3%), and pneumonia (5.8%). In the chemoradiotherapy group, the most common adverse events were leukopenia (9.7%), pneumonia (9.2%), and pleural effusion (3.1%). Serious adverse events occurred in 47.3% and 41.8% of patients, respectively. The 90-day mortality rate after surgery was 3.1% in the FLOT group and 5.6% in the chemoradiotherapy group.
Clinical Implications
The study indicates that perioperative FLOT chemotherapy is a more effective treatment option than preoperative chemoradiotherapy for patients with resectable esophageal adenocarcinoma. However, clinicians should be aware of the higher incidence of adverse events associated with FLOT. As the authors noted, further research is needed to determine the optimal approach for patients who cannot tolerate FLOT due to coexisting conditions or FLOT-related adverse events.
