Neo-AEGIS
Research type
Research Study
Full title
Randomised Clinical Trial of neoadjuvant and adjuvant chemotherapy (Investigator’s choice Modified MAGIC or FLOT regimen) vs. neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junction.
IRAS ID
159662
Contact name
Shaun Preston
Contact email
Sponsor organisation
ICORG- All Ireland Cooperative Oncology Research Group
Eudract number
2011-001858-28
Clinicaltrials.gov Identifier
Duration of Study in the UK
7 years, 0 months, 0 days
Research summary
Cancer of the oesophagus (gullet/food pipe) and oesophagogastric junction (junction between the oesophagus and stomach) have increased in incidence in the West over the last 25 years. Oesophageal cancer is now the 9th most common cancer in the UK, accounting for 3% of all new cases. The aim of this research study is to compare and evaluate two established treatments for oesophageal cancer in order to establish if one treatment is superior to the other. The research group believe it is not currently clear which regimen is of greatest benefit to patients. These 2 regimens have been tested in previous randomised trials (MAGIC & CROSS). The 2 treatments are either chemotherapy before and after surgery, or chemotherapy with radiotherapy before surgery. Both treatments are standard and have been in use as treatments for oesophageal cancer for several years. 594 patients with oesophageal and oesophagogastric junction cancer will be randomly allocated to these 2 treatments. During the trial patients will have a variety of clinical assessments and will complete health-related questionnaires. Following treatment they will be followed up for 3 years. The main objective of this trial is to look at overall survival. Secondary objectives are patient quality of life, complications and relief of swallowing problems.
Summary Results
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfatiYvtk1-2B2gi1K6vKImual9G6VG4-2FeFhNKGHEnJKTVSqZEPbcA9TQeNhWhx1fHtCStW4SqlCcSQNFd7pKyojVWbqWe_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIKXEmFtMmLUbpyyPRXF5u23vhBeYtEyRS6E1RR5O-2BjZhz1kKQQDN3xA162nIeFKKHPpYS7fCYHmZ1TULcTRUGMFYhK7e4FnaD6p9GCgKMkraLGzxAJp4IcIaYVp-2BLX0YU2W0j1HYPRixLQP7QBGeh2VEUD03eHW0OgXqGn1JxT6Q-3D-3D&data=05%7C02%7Cleicestercentral.rec%40hra.nhs.uk%7C71f4026926ef43def19208dc0babc8af%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638398079628229458%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=z%2BgF2oi0ZSKBmZ6DLZJ9giS1VsUAdSMP%2BUbjAe19XVQ%3D&reserved=0
Lay summary of study results: The trial is titled Neo-AEGIS (Neo-adjuvant trial in Adenocarcinoma of the oEsophagus and oesophasoGastric junction Internation Study).
The study was funded by the Health Research Board Ireland, Cancer Research UK (C49462/A18483), Irish Cancer Society, Oesophageal Cancer Fund Ireland and French National Cancer Institut.
Adenocarcinoma (cancer that begins in glandular (secretory) cells) of the oesophagus and oesophagastric junction has dramatically increased in incidence in the world over the last 20 years, probably associated with reflux disease and by the increased prevalence of obesity. It is often advanced at diagnosis, with Stage 3 and Stage 4 the most common at diagnosis, hence it may carry a poor prognosis. The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown, so the trial directly compared two established regimens (treatments). The trial aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently).
Neo-AEGIS (CTRIAL-IE 10-14) was an open-label (treatment given was not concealed from either the researchers or patient), randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage 2-3, nodal stage 0-3, and not metastatic adenocarcinoma of the oesophagus and oesophagogastric junctions were randomly assigned to perioperative chemotherapy or trimodality therapy.
The trial aimed to enrol 540 patients. The trial closed early in December 2020 enrolling 377 patients (184 in the perioperative chemotherapy group and 178 in the trimodality therapy group from 24 centres in 5 countries (Ireland, UK, Denmark, France and Sweden). The trial closed after the second planned interim analysis, on the basis of similar survival metrics in both arms that was unlikely to change and the impact of the COVID-19 pandemic on accrual.
At a median follow up of 38.8 months, median overall survival was 48 months in the perioperative group (MAGIC/FLOT) and 49.2 months in the trimodality therapy group (CROSS), with a 3-year survival probability of 55% and 57%. Median disease-free survival was 32.4 months in the perioperative chemotherapy group and 24.0 months in the trimodality therapy group.
The most common grade 3-4 adverse event was neutropenia (49 of 183 patients in the perioperative chemotherapy group vs 11 of 178 patients in the trimodality group, followed by diarrhoea (20 vs none), and pulmonary embolism (10 v 9).
Due to the trial's early termination the trial results are incomplete and underpowered to make statistical conclusions. However, NeoAEGIS provides the largest comprehensive data on Adenocarcinoma of the oesophagus and oesophagastric junction treated with perioperative chemotherapy (predominantly MAGIC), and CROSS trimodality therapy, and reports similar 3-year survival rates and no major differences in surgical and quality of life questionnaire outcomes. We suggest that these data support continued clinical equipoise and suggest at this time that factors including patient choice, the logistics of combining chemotherapy, radiotherapy, and surgery, which vary from country to country, and access to adjuvant immunotherapy, might be of practical and pragmatic importance in the curative approach to a complex cancer.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
14/EM/1284
Date of REC Opinion
18 Dec 2014
REC opinion
Further Information Favourable Opinion