FLOT4-AIO: trial | Bending the Curve: Trial by Trial

FLOT4-AIO

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

Phase 2/3N = 716NCT01216644

Population

Patients with histologically confirmed locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma: cT2 or higher and/or node-positive, without distant metastases.

Design

Open-label randomised phase 2/3 trial in 38 German hospitals or practice-based oncology settings. Control: three preoperative and three postoperative 3-week cycles of epirubicin and cisplatin with infused fluorouracil or oral capecitabine (ECF/ECX). Experimental: four preoperative and four postoperative 2-week cycles of docetaxel, oxaliplatin, leucovorin and infused fluorouracil (FLOT). The phase 2 part (300 patients enrolled; 265 assessable) had pathological complete regression as primary endpoint; the phase 3 report covers 716 patients (360 ECF/ECX, 356 FLOT), matching the ClinicalTrials.gov enrolment of 716.

Primary endpoint

Arms

ECF/ECX (control, n = 360): Epirubicin, cisplatin and fluorouracil or capecitabine, 3 cycles before and 3 after surgery
FLOT (experimental, n = 356): Docetaxel, oxaliplatin, leucovorin and fluorouracil, 4 cycles before and 4 after surgery

People

Al-Batran SE, senior author FLOT4-AIO Investigators

OSHR 0.77 (95% CI 0.63–0.94)Δ median OS+15 monthsΔ pCR+10 points

Show the numbers

Results reported for FLOT4-AIO
Endpoint	Analysis	FLOT	ECF/ECX	Effect
OS	primaryAl-Batran 2019	median 50 months	median 35 months (27.35–46.26)	HR 0.77 (95% CI 0.63–0.94)The 95% confidence interval for the FLOT median is 38.33 months to not reached (upper limit not a number, so not entered). No P value is given in the abstract.
pCRModified ITT of the phase 2 part: 265 assessable patients (128 FLOT, 137 ECF/ECX)Pathological complete regression (tumour regression grade TRG1a) assessed centrally	interimAl-Batran 2016	16% (10–23%)	6% (3–11%)	P=0.02Primary endpoint of the phase 2 part (pathological complete regression, TRG1a by Becker criteria); the abstract calls this an interim analysis of the phase 2/3 trial.

Results reported for FLOT4-AIO
Endpoint	Analysis	FLOT	ECF/ECX	Effect
OS	primaryAl-Batran 2019	median 50 months	median 35 months (27.35–46.26)	HR 0.77 (95% CI 0.63–0.94)The 95% confidence interval for the FLOT median is 38.33 months to not reached (upper limit not a number, so not entered). No P value is given in the abstract.
pCRModified ITT of the phase 2 part: 265 assessable patients (128 FLOT, 137 ECF/ECX)Pathological complete regression (tumour regression grade TRG1a) assessed centrally	interimAl-Batran 2016	16% (10–23%)	6% (3–11%)	P=0.02Primary endpoint of the phase 2 part (pathological complete regression, TRG1a by Becker criteria); the abstract calls this an interim analysis of the phase 2/3 trial.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.77	0.63–0.94

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

FLOT (experimental)
ECF/ECX (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	FLOT	ECF/ECX
0	100.0%	100.0%
31	65.1%	54.1%
63	41.8%	28.7%
94	27.2%	15.5%
125	17.7%	8.4%

Appears in

2019 FLOT4: perioperative FLOT versus ECF/ECX in gastric and GEJ cancer

Sources

Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948-1957.
PubMed DOI
Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016;17(12):1697-1708.
PubMed DOI