Gastric and gastroesophageal adenocarcinoma survival outcomes relative to completion of perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT): A single-center retrospective analysis.
Authors: Allen Michael J , Espin-Garcia Osvaldo , Panov Elan David , Ma Lucy Xiaolu , Suzuki Chihiro , Bach Yvonne , Darling Gail Elizabeth , Yeung Jonathan , Kalimuthu Sangeetha , Wong Rebecca , Veit-Haibach Patrick , Jang Raymond Woo-Jun , Elimova Elena 
Published: January 2021

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Background: Perioperative FLOT is standard-of-care for locally advanced resectable gastric and gastroesophageal (GEJ) adenocarcinoma. Completion of perioperative chemotherapy (8 cycles) is potentially jeopardised by significant toxicity and intolerance. Only 46% of patients completed all cycles in the initial phase 2/3 trial (FLOT-AIO). We sought to determine the rate of treatment completion in a real-world population and any subsequent impact on survival of incomplete treatment. Methods: A retrospective analysis of gastric and GEJ adenocarcinoma patients treated with perioperative FLOT at Princess Margaret Cancer Centre, Toronto between September 2017 and July 2020 was performed. The rate of perioperative FLOT administration, disease-free survival (DFS) and overall survival (OS) was analysed, with outcomes compared between patients that completed perioperative FLOT and those that didn’t. Results: 32 patients were identified as receiving neoadjuvant FLOT. Mean age was 61.5y, 26 (81%) were male and 29 (91%) were non-Asian. All patients were ECOG 0-1. The median number of neoadjuvant cycles was 4. 29 (91%) had surgery (2 = disease progression; 1 = declined surgery). 10 (34%) patients had minimal/nil response upon resection (College of American Pathologists Tumour Regression Grading (TRG) Score 3), 5 of whom received adjuvant FLOT whilst 5 did not (p0.28). 10 (34%) patients did not receive adjuvant FLOT, 18 (62%) did and 1 received 8 cycles of neoadjuvant chemotherapy. Nil demographic differences were observed between ‘yes’ and ‘no’ adjuvant FLOT groups. The reasons for not having adjuvant chemotherapy were: metastatic disease diagnosed post-operatively (n = 2), TRG Score 3 (n = 4), patient declined further chemotherapy (n = 1), reduced performance status and/or toxicity (n = 2), and the patient requiring treatment for a second malignancy (n = 2). 10 (34%) patients completed perioperative chemotherapy. Median DFS was 12.5m (95% CI 7.9-12.5) for ‘no’ FLOT’ and was not-reached for ‘yes’ FLOT (p = 0.29). 18m DFS was 50% (95% CI 27-93) v 81% (95% CI 64-100) respectively. The median OS for ‘no’ adjuvant FLOT was 16.7m (95% CI 11.5-16.7) with 5 deaths. Zero deaths due to malignancy had occurred at 23.3m in those who received adjuvant FLOT (p0.00164). 1 death in the ‘yes’ group occurred due to interstitial lung disease. Conclusions: In our small population size 34% of patients completed perioperative FLOT. Whilst nil statistically significant difference was observed in mDFS, an improved mOS was observed in those that received adjuvant FLOT suggesting an importance in receiving the maximum number of cycles of chemotherapy. Given the challenges of administering adjuvant FLOT future trials into the feasibility and efficacy of 8 cycles of neoadjuvant FLOT should be considered.