1428P - Total neoadjuvant FLOT chemotherapy in oesophagogastric adenocarcinoma: An international cohort study

Background

Taxane-based triplet perioperative chemotherapy (FLOT) is a standard of care treatment for locally advanced, resectable oesophagogastric adenocarcinoma. However, less than 50% of patients complete all cycles. Delivering all FLOT preoperatively, total neoadjuvant therapy (TNT), may allow more patients to complete treatment but the tolerability, safety and efficacy of TNT are uncertain.

Methods

We carried out a multicentre retrospective analysis of patients diagnosed with oesophagogastric adenocarcinoma between 2015 and 2022 and treated with curative intent with FLOT TNT (1 patient received DCF) followed by surgery at sites in Eastern Europe, North America and United Kingdom. Overall survival was calculated from date of diagnosis to death using the Kaplan-Meier method.

Results

140 patients underwent TNT, 104 with gastric and 36 with oesophageal cancer. The indication for TNT varied between sites. Median age was 61 years and 68% of patients were ECOG PS 0. 118 patients (84%) had AJCC clinical stage 3 or 4a disease. 66 patients (47%) had cT4 disease, of whom 16 had cT4b disease. 116 patients (83%) were cN+. Patients received a median of 8 preoperative cycles with 71% completing all planned chemotherapy and 92% receiving ≥6 cycles. 47% of patients had dose reductions. Surgical resection was carried out in 97% of patients. 30- and 90-day mortality were 2.9% and 4.3%. 79 patients had a complication (56%), of which 27 (19%) had Clavien Dindo grade 3 or 4 complications. Complete pathological regression was observed in 10.7% and ypN0 in 35% of patients. Of the cT4b patients, 50% had ypT4 disease and only one patient was downstaged to

Conclusions

This study demonstrates that TNT can be delivered safely without compromising surgery, with surgical morbidity and mortality comparable to perioperative trial outcomes. Survival outcomes are encouraging considering the advanced stage of the patient cohort; however, outcomes for cT4b remain sub-optimal. Prospective evaluation of TNT is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

International Oesophagogastric TNT Collaborative Group.

Funding

Has not received any funding.

Disclosure

E.C. Smyth: Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Imedex, Merck, Novartis, Prova Education, Servier, TouchIME, Elsevier, Peervoice, Cor2Ed, Daiichi Sankyo, MSD, Suzhou Liangihui Network Technology Company Ltd; Financial Interests, Personal, Other, TSC: Amgen; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol Myers Squibb, Bristol Myers Squibb, My Personal Therapeutics, Novartis, Roche, Servier, Zymeworks, Viracta, Boehringer Ingelheim, AbbVie, Natera; Financial Interests, Personal, Other, IDMC: BeiGene, Zymeworks; Financial Interests, Personal, Other, IDMC chair: Everest Clinical Research; Financial Interests, Personal, Other, IDMC Chair: Jazz Pharmaceuticals; Financial Interests, Personal, Officer: EORTC GI Clinical Trials Group; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Merus, Basilea, MSD, Mirati; Financial Interests, Institutional, Coordinating PI: Roche, AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca; Non-Financial Interests, Leadership Role, Trustee: UK & Ireland Oesophagogastric Group (UKIOG). R.D. Petty: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BMS, Servier, Astellas; Financial Interests, Personal, Invited Speaker: BMS, Servier; Financial Interests, Personal, Other, Travel grant: BMS, MSD; Financial Interests, Institutional, Funding: Amgen, Basilea, AstraZeneca, BMS, Five Prime Therapeutics, Platinum Therapeutics, Roche, MSD, Moderna, Astellas. All other authors have declared no conflicts of interest.