Impact of relative dose intensity (RDI) of perioperative FLOT in resectable and locally advanced gastric and gastroesophageal junction adenocarcinoma.

Abstract

e24089 Background: Perioperative FLOT is the standard of care for resectable locally advanced gastric (GC) and gastro-oesophageal junction (GEJ) adenocarcinoma, but the compliance is frequently suboptimal due to toxic side effects, resulting in dose reductions and treatment delays. RDI represents the proportion between the delivered dose intensity (DDI) of chemotherapy and the standard dose intensity (SDI). While there is well-documented evidence highlighting the importance of RDI in patients with different types of cancer, data specific to those with GC and GEJ adenocarcinoma remain scarce. In this study, we assessed the impact of RDI in perioperative FLOT on the outcomes of patients with resectable and locally advanced GC and GEJ adenocarcinoma. Methods: A retrospective analysis of GC and GEJ adenocarcinoma patients undergoing perioperative FLOT in a single institution in Italy between 2019 and 2023 was performed. RDI was calculated by dividing the DDI by SDI for each drug and the triplet. Relapse-free survival (RFS) and overall survival (OS) outcomes were analyzed between higher RDI (>75%) and lower ( < 75%) groups. Results: 113 patients (median age, 66 years; range: 35-79 years) were included. 33 patients received RDI>75% while 80 received RDI < 75%. The median follow-up was 33 months (95% CI: 30.5-38.7). For overall population, mRFS was 73.2 months (mos) (95% CI: 25.7-NR) and mOS was 72.2 mos (95% CI: 72.2-NR). 12/113 (10.6%) patients achieved pathological complete response (pCR). There was no statistically significant difference between RDI>75% and RDI < 75% groups considering FLOT regimen both for mRFS (NR vs 73.2 mos, HR: 1.06 95% CI: 0.56-2.02, p = 0.86) and mOS (NR vs 72.2 mos, HR: 1.34 95% CI: 0.55-3.24, p = 0.52). These results were consistent also considering individual drugs, both in terms of mRFS for 5-fluorouracil (73.1 vs NR mos, HR: 1.30 95% CI: 0.60-2.82, p = 0.5), oxaliplatin (73.1 vs 26.3 mos, HR: 0.68 95% CI: 0.37-1.25, p = 0.21), docetaxel (NR vs 73.2 mos, HR: 0.88 95% CI: 0.47-1.69, p = 0.71) and in terms of mOS for 5-fluorouracil (84.4 vs 72.2 mos, HR: 1.09 95% CI: 0.37-3.2, p = 0.88), oxaliplatin (84.4 vs 72.2 mos, HR: 0.75 95% CI: 0.32-1.74, p = 0.5), and docetaxel (NR vs 72.2 mos, HR: 1.10 95% CI: 0.46-2.67, p = 0.83). Hematological G3-4 adverse events (AEs) occurred in 9% and 21.3% of patients with RDI>75 and RDI < 75, respectively (OR: 0.37 95% CI: 0.10 to 1.37, p = 0.14). Gastrointestinal G3-4 AEs occurred in 3% and 11,3% of patients with RDI>75 and RDI < 75, respectively (OR: 0.25, 95% CI: 0.03 to 2.02, p = 0.20). Conclusions: In real-world practice, even when dose reductions are required due to toxicity, a lower RDI does not significantly affect RFS or OS for any individual drug or the FLOT regimen in patients with GC and GEJ adenocarcinoma. Therefore, further studies on dose optimization in selected cases are warranted using larger datasets.