Updated results of the FLOT4-AIO trial (abstract LBA27_PR) confirmed the superiority of a docetaxel-based triplet regimen over the current standard of care in patients with resectable esophagogastric cancer. Docetaxel, oxaliplatin, and fluorouracil (5-FU)/leucovorin (FLOT) improved outcomes compared with epirubicin, cisplatin, and 5-FU (ECF) or epirubicin, cisplatin, and capecitabine (ECX) across all subgroups investigated.
The results were presented by Salah-Eddin Al-Batran, MD, director of the Institute of Clinical Cancer Research at UCT-University Cancer Centre, Krankenhaus Nordwest in Frankfurt, Germany, at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid.
In the FLOT4 trial, 716 patients with resectable gastric or gastroesophageal junction adenocarcinoma were randomly assigned to either 3 preoperative and 3 postoperative 3-week cycles of ECF/ECX (epirubicin 50 mg/m2 and cisplatin 60 mg/m² both on day 1, and 5-FU 200 mg/m² or capecitabine 1,250 mg/m2 orally on days 1 to 21) or 4 preoperative and 4 postoperative 2-week cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m², 5-FU 2,600 mg/m², and leucovorin 200 mg/m² all on day 1). The primary endpoint was overall survival.
Previously reported results showed that the docetaxel-containing regimen was associated with less progressive cases during and after preoperative therapy (1% vs 5%; P < .001), more R0 resections (84% vs 77%; P = .011), and a higher number of pT0/pT1 tumors (25% vs 15%; P = .001). The FLOT regimen significantly delayed progression (30 vs 18 months; hazard ratio [HR], 0.75; P = .001) and extended overall survival (50 vs 35 months; HR, 0.77; P = .012) compared with the ECF/ECX regimen.
The updated results presented at ESMO showed that the increased efficacy of FLOT was seen in all subgroups, including the elderly and patients with signet cell tumors. In addition, it was numerically pronounced in Siewert type 1 esophageal tumors (HR, 0.60), Barrett tumors (HR, 0.62), small tumors T1/2 (HR, 0.66), and node-negative tumors (HR, 0.64).
Multivariable analyses identified certain parameters associated with favorable survival, including FLOT therapy (HR, 0.75; P = .006), stomach as the primary tumor (HR, 0.74; P = .005), and nodal negativity (HR, 0.72; P = .022).
“These new analyses confirm the superiority of FLOT, which is the new standard of care in the perioperative treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma,” said Al-Batran, in a press release.
Commenting for ESMO, Michel Ducreux, MD, PhD, head of the gastrointestinal oncology unit at the Institut Gustave Roussy in Villejuif, France, said, “The triplet regimen used in the FLOT4 trial was developed to improve the results of ECF. It decreased toxicity by replacing epirubicin with low-dose docetaxel, and using oxaliplatin instead of cisplatin. FLOT is also more convenient to use, with one 24-hour infusion every 2 weeks rather than continuous infusion of 5-FU in the ECF protocol.”
“The results show that FLOT is clearly the new standard of care,” continued Ducreux. “FLOT will be the best backbone of chemotherapy that we can use in this setting. A step forward would be to try to improve the results by adding targeted therapies or immune checkpoint inhibitors. It would also be interesting to know if the FLOT regimen shows different levels of effectiveness in the four molecular biological subgroups of gastric cancer.”