Modified FLOT regime outperforms FOLFOX in advanced/metastatic gastric/gastroesophageal junction adenocarcinoma

In participants with advanced HER2-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, a modified FLOT regimen (mFLOT) demonstrated significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) versus FOLFOX, as was demonstrated by the GASTFOX study.

The preferred first-line chemotherapy regimen for irresectable locally advanced or metastatic G/GEJ adenocarcinoma is a platinum/fluoropyrimidine combination, such as FOLFOX [1]. For localised G/GEJ adenocarcinomas, perioperative FLOT triplet has become the standard of care [2]. The current phase 3 GASTFOX study (NCT03006432) explored the efficacy and safety of mFLOT with a modified dose of 5FU (2400 mg/m²/46 hr) versus FOLFOX in participants with advanced G/GEJ adenocarcinomas [3].

GASTFOX randomised 506 participants with HER2-negative, locally advanced unresectable or metastatic G/GEJ adenocarcinoma 1:1 to FOLFOX or mFLOT. The primary endpoint was PFS and the secondary endpoints included OS and safety. For survival outcomes, HR and 95% CI were estimated by a Cox proportional hazard (PH) model. In the case of non-PH, the restricted mean survival time was used to evaluate the treatment effect. Prof. Aziz Zaanan (Université Paris Cité, France) presented the results [4].

After a median follow-up of 42.8 months, PFS was in favour of mFLOT with 7.59 versus 5.98 months (non-PH). Restricted mean survival time at 12 months was 7.52 versus 6.62 months (P=0.007). mFLOT also significantly improved OS: 15.08 versus 12.65 months (HR 0.82; 95% CI 0.68–0.99; P=0.04).

“In participants with advanced HER2-negative G/GEJ adenocarcinoma, mFLOT demonstrated significant and clinically meaningful improvement in PFS and OS versus FOLFOX,” said Prof. Zaanan. “Therefore, mFLOT can be considered as a new therapeutic option for patients eligible for a triplet regimen.”

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   1. Lordick F, et al. Ann Oncol. 2022;33(10):1005–1020.
   2. Al-Batran S-A, et al. Lancet. 2019;391(10184):1948–1957.
   3. Van Cutsem E, et al. Ann Oncol. 2015;26(1):149–156.
   4. Zaanan A, et al. 5-fluorouracil and oxaliplatin with or without docetaxel in the first-line treatment of HER2 negative locally advanced (LA) unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma (GASTFOX-PRODIGE 51): A randomized phase III trial sponsored by the FFCD. Abstract LBA77, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 19 December, 202327 March, 2024