1402MO - An international study evaluating pathological response to guide adjuvant FLOT chemotherapy in gastroesophageal cancer

Background

The majority of patients are unable to complete all planned adjuvant FLOT therapy in locally-advanced gastroesophageal cancers. We examined whether pathological response to neoadjuvant FLOT can guide its adjuvant use.

Methods

Prospectively collected data from 43 centres across 12 countries was analysed. Patients with non-metastatic gastroesophageal adenocarcinoma who received neoadjuvant FLOT followed by radical surgery between 2017-2022 were included. Pathological response was assessed using validated tumour regression grading (TRG) systems. All TRG were trichotomized into minimal responders (MR=worse TRG category), complete responders (CR=pathological complete response), and partial responders (PR=all TRG categories between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT within these cohorts were compared using Kaplan Meier and Cox regression analysis.

Results

1887 patients (MR n=459, CR n=221, PR n=1207) were evaluated. The median follow-up was 25.5 (IQR 15.0-39.0) months. 82.9% and 75.8% of patients completed all 4 cycles neoadjuvant and adjuvant FLOT respectively. Prognostic pathological features were similar between those who did and did not receive adjuvant FLOT. In the MR group, there was no DFS difference (HR 1.03, 95% CI 0.78-1.36) between those who did (n=272) and did not (n=187) receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS (HR 0.73, 95% CI 0.55-0.97), this became insignificant after adjusting for baseline characteristics (HR 0.96, 95% CI 0.70-1.30). In the CR group, there was no difference in DFS (HR 0.88, 95% CI 0.41-1.85) or OS (HR 0.69, 95% CI 0.31-1.54) between those who did (n=136) and did not (n=85) receive adjuvant FLOT. In the PR group (adjuvant FLOT n=847, no adjuvant FLOT n=360), adjuvant FLOT conferred a significant DFS (HR 0.68, 95% CI 0.55-0.86) and OS (HR 0.55, 95% CI 0.44-0.69) benefit.

Conclusions

Pathological response to neoadjuvant FLOT predicts therapeutic efficacy to adjuvant FLOT. Only partial responders benefit from adjuvant treatment. This challenges the current doctrine that perioperative FLOT should be applied to all patients regardless of pathological tumour response.

Clinical trial identification

ACTRN12622000180718.

Editorial acknowledgement

Legal entity responsible for the study

Peter MacCallum Cancer Centre.

Funding

Royal Australasian College of Surgeons.

Disclosure

All authors have declared no conflicts of interest.