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Perioperative chemotherapy outperforms neoadjuvant chemoradiation in resectable oesophageal cancer

Presented by
Prof. Jens Höppner, Universität Bielefeld, Germany
ASCO 2024
Phase 3, ESOPEC
Perioperative chemotherapy (FLOT regimen) plus surgery improves overall survival compared with neoadjuvant chemoradiation (CROSS regimen) plus surgery for patients with resectable oesophageal adenocarcinoma, as shown in the ESOPEC trial.

Multimodality treatment is standard-of-care for patients with non-metastatic, resectable oesophageal adenocarcinoma. In the past decade, 2 different multimodality regimens were developed: the CROSS regiment (neoadjuvant chemoradiation followed by surgery) and the FLOT regimen (preoperative chemotherapy, surgery, postoperative chemotherapy) [1,2]. The phase 3 ESOPPEC trial (NCT02509286) aimed to perform a head-to-head comparison of the CROSS regimen versus the FLOT regimen. Prof. Jens Höppner (Universität Bielefeld, Germany) presented the results. [3].

ESOPEC enrolled 483 patients with resectable oesophageal adenocarcinoma (80% cT1-2, 20% cT3-4; 20% cN0, 80% cN+). Patients were randomised 1:1 to FLOT (4 cycles FLOT-4, surgery, 4 cycles FLOT-4) or CROSS (41.4 Gy, 5 cycles paclitaxel/carboplatin, surgery). The primary endpoint was overall suvival (OS).

After a median follow-up of 55 months, the median OS in the FLOT arm was 66 months (95% CI 36-ne) versus 37 months (95% CI 28-43) in the CROSS arm (HR 0.70; 95% CI 0.53-0.92; P=0.012). The 3-year OS rate was 57.4% and 50.7%, respectively. The OS was in favour of FLOT in all subgroups: age, sex, clinical T-stage, and clinical N-stage. FLOT also favoured median PFS, with 38 months (95% CI 21-ne) versus 16 months (95% CI 12-22), and a 3-year PFS rate of 51.6% versus 35.0%.

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

‚ÄúIn patients with cT1-4a resectable oesophageal adenocarcinoma, the FLOT regimen plus surgery improved OS compared with the CROSS regimen plus surgery,‚ÄĚ concluded Prof. H√∂ppner. Commenting on this presentation, Dr Karyn Goodman (Mount Sinai, NY, USA) noted 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. 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). 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.

Medical writing support was provided by Marten Dooper, PhD.

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