The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Perioperative chemotherapy induces equivalent efficacy as neoadjuvant multimodal therapy in patients with locally advanced adenocarcinoma of the esophagus and esophagogastric junction.

The optimum combination curative approach for patients with adenocarcinoma of the esophagus and esophagogastric junction is currently unknown. A key question is whether neoadjuvant multimodal therapy, specifically carboplatin/paclitaxel plus 41.4Gy radiation therapy (CROSS), is superior to optimum perioperative chemotherapeutic regimens, including the well-established modified MAGIC regimen (epirubicin, cisplatin [oxaliplatin], 5-FU [capecitabine]) and, more recently, FLOT (docetaxel, 5-FU, leucovorin, and oxaliplatin).

“Neo-AEGIS (Neoadjuvant trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study) is designed as the first randomized controlled trial to address this question,” said lead author John V. Reynolds, BCh, FRCS, MA, MB, MCh, of Cancer Trials Ireland and St James’s Hospital. He presented the results of the study at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

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Researchers randomly assigned 377 patients to receive CROSS or perioperative chemotherapy (ECF/ECX/EOF/EOX pre-2018, FLOT option 2019/20) at 24 sites in Ireland, the United Kingdom, Denmark, France, and Sweden. The primary outcome was overall survival. Secondary endpoints included toxicity, pathologic measures of response, and postoperative complications as per the Esophageal Complications Consensus Group (ECCG) definitions and Clavien-Dindo severity grade.

Of 362 evaluable patients (median age, 64 years), 178 patients received CROSS (arm A) and 184 patients received MAGIC/FLOT (157 patients/27 patients; arm B). The majority of patients included in the trial were male (90%) and had cT3 disease (84%) or cN1 disease (58%).

At a median follow up of 24.5 months, there were 143 deaths (70 in the CROSS arm and 73 in the MAGIC/FLOT arm). “The 3-year estimated overall survival was almost identical in the 2 arms (56% CROSS arm and 57% MAGIC/FLOT arm),” said Reynolds. Based on the absence of futility evidenced in this data, the Data and Safety Monitoring Board recommended closure of recruitment in December 2020. Final assessment of the study is expected in 2022.

“The pathological response rate was hugely significantly in favor of the CROSS arm in terms of node-negativity, changing from node-positive to node-negative, and in margin status,” said Reynolds. Pathological complete response and major pathological response were also higher in the CROSS arm than the MAGIC/FLOT arm.

There were no differences in complications between the arms. Five patients died in the CROSS arm and 3 patients died in the MAGIC/FLOT arm.

 “This randomized controlled trial reveals no evidence that perioperative chemotherapy is unacceptably inferior to multimodal therapy,” concluded Reynolds. “There is no reason this association will not continue. It’s highly probable that arm A will remain non-inferior to arm B. These data strongly suggest non-inferiority and support equipoise in decision-making in modern practice.”

Disclosure: This research was supported by Health Research Board Ireland, Cancer Research UK (C49462/A18483), Irish Cancer Society, Oesophageal Cancer Fund Ireland. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Reynolds JV, Preston SR, O’Neill B, et al. Neo-AEGIS (Neoadjuvant trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): Preliminary results of phase III RCT of CROSS versus perioperative chemotherapy (Modified MAGIC or FLOT protocol). (NCT01726452). J Clin Oncol. 2021;39:(suppl 15; abstr 4004). doi:10.1200/JCO.2021.39.15_suppl.4004