FLOT outperforms CROSS in resectable oesophageal cancer

Perioperative chemotherapy (FLOT regimen) plus surgery improved overall survival (OS) compared with neoadjuvant chemoradiation (CROSS regimen) plus surgery for patients with cT1cN⁺ and cT2-4a, cN^-/+ resectable oesophageal adenocarcinoma in the phase 3 ESOPEC trial.

Multimodality treatment is the standard treatment for non-metastatic, resectable oesophageal adenocarcinoma. In the past decade, 2 different multimodality regimens have been developed: the CROSS regimen (neoadjuvant chemoradiation followed by surgery) and the FLOT regimen (pre-operative chemotherapy, surgery, post-operative chemotherapy) [1,2].

The phase 3 ESOPEC trial (NCT02509286) aimed to compare the CROSS and FLOT regimens head-to-head. Prof. Jens Höppner (University of Bielefeld, Germany) presented the results [3]. ESOPEC enrolled 483 participants with resectable oesophageal adenocarcinoma (80% cT1-2, 20% cT3-4; 20% cN0, 80% cN⁺) and randomised them 1:1 to the FLOT regimen (i.e. 4 cycles FLOT-4, surgery, 4 cycles FLOT-4) or the CROSS regimen (i.e. 41.4 Gy, 5 cycles paclitaxel/carboplatin, surgery). The primary endpoint was OS.

After a median follow-up of 55 months, the median OS in the FLOT arm was 66 months, versus 37 months in the CROSS arm (HR 0.70; 95% CI 0.53–0.92; P=0.012; see Figure). The 3-year OS rates were 57.4% and 50.7%, respectively. OS also favoured FLOT in all defined subgroups (i.e. age, sex, clinical T category, clinical N category). Median PFS was 38 months with FLOT versus 16 months with CROSS, and 3-year PFS rates were 51.6% and 35.0%, respectively.

Figure: Overall survival in ESOPEC [3]



Comparable rates in both arms were observed for resection status (95% R0), post-operative N category (50% ypN0), and post-operative complications (23% Clavien-Dindo grade III, 1% 30-day mortality). Pathological complete remission was lower with CROSS than with FLOT (10% vs 16.8%).

“In patients with cT1-4a resectable oesophageal adenocarcinoma, the FLOT regimen plus surgery improves OS compared with the CROSS regimen plus surgery,” concluded Prof. Höppner. Commenting on this presentation, Dr Karyn Goodman (Mount Sinai Hospital, NY, USA) pointed out that the original CROSS trial demonstrated significantly better outcomes compared with the CROSS arm of ESOPEC. In addition, adjuvant immunotherapy after the CROSS regimen can improve survival [4].

1. Van Hagen P, et al. N Engl J Med 2012;366:2074-2084.
2. Al Batran S-E,et al. Lancet 2019;393:1948-1957.
3. Höppner J, et al. Perioperative chemotherapy (FLOT) versus neoadjuvant chemoradiotherapy (CROSS) for resectable esophageal adenocarcinoma. Abstract LBA1, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.
4. Kelly RJ, et al. N Engl J Med 2021;384:1191-1203.

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Posted on 18 July 202419 July 2024