The superiority of docetaxel based triplet therapy over standard care in patients with resectable esophago-gastric cancer has been confirmed in late-breaking results from the FLOT4 trial presented at the ESMO 2017 Congress in Madrid.1

Survival in resectable esophago-gastric cancer is poor. Five-year overall survival is around 25% with surgery, and is increased to 36% by adding a perioperative regimen of epirubicin, cisplatin, and infused fluorouracil (ECF). (2) Phase II studies have shown encouraging pathological response rates with perioperative docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT).

The phase III FLOT4 trial randomised 716 patients with resectable gastric or gastroesophageal junction adenocarcinoma to perioperative FLOT or ECF. As previously reported, FLOT was superior to ECF for all efficacy endpoints including curative resection rates, progression-free survival and overall survival.  Specifically Compared to ECF, FLOT was associated with less progressive disease, more surgical resections and an improvement of both overall survival and survival without cancer progression. FLOT treated patients survived without cancer progression an average of 30 months compared to 19=8 months of ECF and experienced average overall survival of 50 vs. 35 months.

Today researchers reveal the results of multivariate, subgroup and sensitivity analyses for the first time. The relative effect of FLOT was observed in all subgroups, including the elderly and signet cell cancers, and was particularly pronounced in Siewert type 1 esophageal cancer and Barretts cancers.

This new analyses confirms the superiority of FLOT, which should be the new standard of care in the perioperative treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma.  A step forward would be to try to improve the results by adding targeted therapies or immune checkpoint inhibitors, which have recently been shown to have promising activity in the treatment of gastric cancer.

References

1. Abstract LBA27_PR ‘Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: updated results from multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO).
2. Cunningham D, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.

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