Results of the observational prospective RealFLOT study

Elisa Giommoni,Marco Brugia,Serena Pillozzi,Marco Puzzoni,Daniele Lavacchi,Francesco Iachetta,Luca Pompella,Carmelo Pozzo,Vincenzo Formica,Ferdinando De Vita,Michele Prisciandaro,Michele Sisani,Andrea Spallanzani,Filippo Giovanardi,Giuseppe Tirino,Maria Antonietta Satolli,Alessandra Romagnani,Samantha Di Donato,Irene Pecora,Silvia Stragliotto,Antonia Strippoli,Sara Fancelli,Lorenzo Fornaro,Lorenzo Antonuzzo

doi:10.1186/s12885-021-08768-7

Abstract

BackgroundPerioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone.MethodsRealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status.ResultsOf 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3–4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients.ConclusionsThese real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets.

Highlights

Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone
Perioperative CT became a standard of care in Europe for resectable GC based on the results of the MAGIC [2] and FNCLCC/FFCD 9703 [3] trials that showed a significant improvement in overall survival (OS) for patients treated with preoperative CT, as compared with surgery alone
The study population consisted of patients with histologically confirmed diagnosis of gastric or gastro-oesophageal junction (GEJ) adenocarcinoma with clinical stage cT2 or higher and/or nodal involvement referring to the 7th edition of the International Union Against Cancer Tumour–Node–Metastasis classification, and suitable to underwent a R0-R1 resection, according to local surgical evaluation [10]

Summary

Introduction

Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone. Perioperative CT became a standard of care in Europe for resectable GC based on the results of the MAGIC [2] and FNCLCC/FFCD 9703 [3] trials that showed a significant improvement in overall survival (OS) for patients treated with preoperative CT (epirubicin, cisplatin, and 5-fluorouracil [ECF] in MAGIC trial and cisplatin, and 5-fluorouracil in FNCLCC/FFCD trial), as compared with surgery alone. Docetaxel-based modified regimens as FLOT, consisting of 5-fluorouracil, leucovorin, oxaliplatin and docetaxel, have proved to be active in terms of complete pathological regression and to be more tolerable than classical DCF [6,7,8]

Methods

Results

Discussion

Conclusion