270. PERIOPERATIVE CHEMOTHERAPY FOR OPERABLE GASTRO-ESOPHAGEAL JUNCTION OR GASTRIC CANCER: FLOT VERSUS ANTHRACYCLINE TRIPLETS

Abstract Background Since the FLOT4-AIO study (2019) showed improved survival in patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) compared to those treated with neoadjuvant anthracycline triplets, FLOT became standard of care in the Netherlands and most Western countries. The aim of this study was to compare the overall survival (OS), pathological response and surgical outcomes of FLOT chemotherapy to anthracycline triplets in the Netherlands, using real-world population level data. Methods Patients diagnosed with resectable (cT2-4a/cTxN0–3/NxM0) gastro-esophageal junction and gastric carcinoma between 2015–2020 were selected from the Netherlands’ Cancer Registry. Patients were included if they received neoadjuvant FLOT or anthracycline triplets whether this was followed by resection or not. OS was calculated from start of neoadjuvant therapy, analyzed using cox regression analysis and adjusted for sex, age, comorbidities, performance status, cT-stage/cN-stage and tumor grade. Secondary outcomes included the pathological complete response (pCR), proportion of patients that fully completed neoadjuvant chemotherapy (100% of scheduled cycles permitting dose reductions), proportion of patients that underwent (radical) surgical resection and proportion receiving adjuvant therapy. Results 778 included patients were treated with FLOT and 913 with anthracycline triplets. Patients treated with FLOT underwent more staging diagnostic laparoscopies (DLS) (73.5% vs. 44.1%, p < 0.0001). Adjusted OS was better after neoadjuvant FLOT (HR = 0.84, 95% CI 0.72–0.98, p = 0.03). 3-year and 5-year OS were 56.4% and 46.6% after FLOT and 52.7% and 45.5% after anthracycline triplets, respectively. A higher proportion of patients treated with FLOT fully completed neoadjuvant chemotherapy (78.5% vs. 73.1%, p = 0.009) and had R0 resections (86.2% vs. 85.2%, p = 0.007). No statistically significant differences were seen in the proportions of patients that underwent resection, received adjuvant therapy, or had pCR. Conclusion Real-world population level data showed better OS of patients treated with FLOT chemotherapy compared to anthracycline triplets. No statistically significant difference was observed in pCR or resection rates. Thus, not every outcome as described in the FLOT4-AIO trial could be reproduced in a real-world population, despite improved staging with DLS in the FLOT group. Divergent baseline characteristics and less intensive neoadjuvant treatments in real-world patients compared to patients in clinical trials may contribute to this discrepancy.