CROSS versus modified MAGIC or FLOT in oesophageal and gastro-oesophageal junction adenocarcinoma.

The optimal management of locally advanced oesophageal and gastro-oesophageal junction adenocarcinoma has remained a subject of ongoing debate for several years. In The Lancet Gastroenterology & Hepatology, John V Reynolds and colleagues report the results of the phase 3 Neo-AEGIS trial comparing 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) with trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) in 362 patients with oesophageal or gastro-oesophageal junction adenocarcinoma. With a 3-year overall survival rate of 55% (95% CI 47–62) with perioperative chemotherapy versus 57% (49–64) with trimodality therapy (hazard ratio 1·03 [95% CI 0·77–1·38]; log-rank p=0·82), the Neo-AEGIS trial benchmarks the outcomes after contemporary high-quality multimodality treatment. 1 Reynolds JV Preston SR O'Neill B et al. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial. Lancet Gastroenterol Hepatol. 2023; (published online Sept 18.)https://doi.org/10.1016/S2468-1253(23)00243-1 Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Other outcomes, including disease-free survival, recurrence patterns, and operative results, also showed no significant differences between the CROSS and MAGIC or FLOT regimens. With FLOT being administered to just 15% of patients in the perioperative chemotherapy group, the comparison between CROSS versus FLOT awaits resolution through the forthcoming results of the ESOPEC trial (NCT02509286). Until then, Neo-AEGIS strongly suggests clinical equipoise. This proposition is supported by a recent individual participant data network meta-analysis of four previous randomised trials (including a total of 497 patients) on neoadjuvant chemoradiotherapy versus chemotherapy (hazard ratio for overall survival 0·90 [95% CI 0·74–1·09]). 2 Faron M Cheugoua-Zanetsie M Tierney J et al. Individual participant data network meta-analysis of neoadjuvant chemotherapy or chemoradiotherapy in esophageal or gastroesophageal junction carcinoma. J Clin Oncol. 2023; (published online July 12.)https://doi.org/10.1200/JCO.22.02279 Crossref PubMed Scopus (1) Google Scholar Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trialAlthough underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise. Full-Text PDF Open Access