Perioperative chemotherapy with a docetaxel-based triplet should be considered the new standard of care for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to the multicenter randomized phase III FLOT4 trial. The results (abstract 4004) were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.
The MAGIC trial established perioperative epirubicin, cisplatin, and fluorouracil (ECF) as a standard treatment for patients with operable esophagogastric cancer. However, outcomes remain unsatisfactory, with a median survival of 25 months and a 5-year survival rate of 36%, said Salah-Eddin Al-Batran, MD, of the Institute of Clinical Cancer Research at Krankenhaus Nordwest, UCT-University Cancer Center in Frankfurt.
“In two phase II trials, our group demonstrated that the docetaxel-based triplet FLOT (docetaxel, oxaliplatin, and fluorouracil/leucovorin) was tolerable and associated with encouraging rates of pathologic response in patients with gastric and GEJ adenocarcinoma,” said Al-Batran.
The trial randomized 716 patients, with a median age of 62 years, to either the docetaxel-based triplet FLOT (356 patients) or the anthracycline-based triplet ECF/ECX (epirubicin, cisplatin, and capecitabine) (360 patients).
Patients received either 3 preoperative and 3 postoperative 3-week cycles of ECF/ECX or 4 preoperative and 4 postoperative 2-week cycles of FLOT. The primary endpoint was overall survival (OS).
Baseline characteristics were similar between arms overall, noted Al-Batran. In the ECF/ECX arm, 91% of patients completed planned preoperative cycles and 37% completed planned postoperative cycles; in the FLOT arm, 90% and 46% did, respectively.
After a median follow-up of 43 months, 369 patients died (203 in the ECF/ECX arm and 166 in the FLOT arm).
The median OS was higher in the FLOT group (median, 50 months) compared with the ECF/ECX group (median, 35 months). The 3-year OS rate was 57% with FLOT and 48% with ECF/ECX. FLOT also improved progression-free survival (PFS), with a median PFS of 30 months vs 18 months with ECF/ECX.
“FLOT increased rates of curative surgery and prolonged PFS and OS as compared to ECF/ECX,” said Al-Batran, adding that the relative effect from FLOT was consistent across subgroups and sensitivity analyses.
Half the patients in both arms experienced perioperative complications. The 30-day and 90-day mortality rate was 3% and 8% with ECF/ECX and 2% and 5% with FLOT, respectively.
There was more grade 3/4 nausea and vomiting with ECF/ECX and more grade 3/4 neutropenia with FLOT.
“With FLOT, there was no increase in surgical morbidity and mortality, re-surgeries, and hospitalization time,” reported Al-Batran. “FLOT improved outcome in patients with resectable gastric and GEJ cancer compared to perioperative ECF/ECX. It is a new standard of care in perioperative treatment of patients with adenocarcinoma of the stomach or GEJ.”