KEY TAKEAWAYS
- The ESOPEC phase 3 trial aimed to compare the relative efficacy of FLOT & CROSS against EAC.
- The primary endpoint was the OS.
- The results revealed that the preoperative FLOT demonstrated improved survival results in patients with resectable EAC vs neoadjuvant CROSS.
ESOPEC (NCT02509286) is a pivotal phase 3 trial comparing neoadjuvant chemoradiation therapy (CROSS regimen-combined chemotherapy and radiotherapy) with perioperative chemotherapy (FLOT regimen-administration of chemotherapy before and after the surgery) for resectable esophageal adenocarcinoma (EAC). CROSS (carboplatin/paclitaxel) was targeted to reduce the size of the tumor before the surgical procedure. Contrarily, the FLOT regimen (5-FU, leucovorin, oxaliplatin, docetaxel) aimed at minimizing the spread of cancer.
Jens Hoeppner and the other researchers intended to perform a comparative analysis between 2 major multimodal treatment strategies for resectable locally advanced EAC.
The study enrolled patients (pts) with resectable esophageal adenocarcinoma (EAC) classified as cT1 cN+ cM0 or cT2-4a cNany cM0. The primary endpoint is overall survival (OS), with 90% power to detect an HR of 0.645, requiring 218 events at a one-sided significance level of 2.5%. An intention-to-treat analysis was conducted for all randomized pts. The treatment’s effect on OS was estimated using Cox regression, stratified by study site, and included N stage (N0, N+) and age as covariates.
About 438 pts from 25 diverse locations in Germany were randomly divided into 2 treatment groups, 221 to FLOT and 217 to CROSS. Baseline characteristics, including male sex (89.3%), median age of 63 years (range 30-86), cT3/4 staging (80.5%), and cN+ status (79.7%), were well balanced between both arms.
In 403 pts, the neoadjuvant treatment started, of which 207 pts were subjected to FLOT and 196 pts to CROSS, while the surgery was performed in 371 pts (191 FLOT; 180 CROSS). R0 resection was achieved in 351 patients (180 FLOT; 171 CROSS). 90 days post-surgery, the mortality rate stood at 4.3%, with 3.2% occurring in the FLOT group and 5.6% in the CROSS group.
Over a follow-up period of 55 months, a sum of 218 pts had passed away (97 FLOT; 121 CROSS). Median (OS) was 66 (95% CI 36 – not estimable) for the FLOT arm, and 37 (95% CI 28 – 43) months for the CROSS group. The 3-year OS rates were 57.4% (95% CI 50.1 – 64.0%) for FLOT and 50.7% (95% CI 43.5 – 57.5%) for CROSS, with an HR) of 0.70 (95% CI 0.53-0.92, P=0.012). The complete pathological response was seen in 35 (19.3%, 95%-CI 13.9 – 25.9%) of pts in the FLOT group and 24 (13.5%, 95%-CI 8.8 – 19.4%) in the CROSS group, out of 359 pts with a physiological status of assessable tumor regression.
The research concluded that perioperative FLOT exhibited enhanced survival rates in resectable EAC relative to neoadjuvant CROSS.
The trial was sponsored by DFG- Deutsche Forschungsgemeinschaft.
Source: https://meetings.asco.org/abstracts-presentations/234899
Clinical Trial: https://www.clinicaltrials.gov/study/NCT02509286
Hoeppner J, Brunner T, Lordick F, et al. (2024). “Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 17; abstr LBA1), DOI: 10.1200/JCO.2024.42.17_suppl.LBA1
