Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as perioperative treatment for patients with HER2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the AIO Gastric Cancer Study Group.

Perioperative chemotherapy with FLOT is a mainstay in the treatment of esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in patients (pts) with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in patients with locally advanced EGA. A multicenter phase II study evaluated the efficacy and toxicity of perioperative FLOT (24-h 5-FU 2,600 mg/m2 , leucovorin 200 mg/m2 , oxaliplatin 85mg/mg2 , docetaxel 50 mg/m2 , trastuzumab 6mg/kg then 4 mg/kg d1, repeated d15 for four cycles pre- and postoperatively followed by 9 cycles of trastuzumab monotherapy) in patients with HER-2 positive EGA. Pts had ≥cT2, any N, M0 EGA. The primary endpoint was the rate of centrally assessed pathological complete response (pCR). Secondary endpoints comprised disease-free (DFS) and overall survival (OS), R0 resection rate, toxicity and surgical morbidity. 56 evaluable pts (median age 62 years) were included. n=40 had tumors originating from the esophagogastric junction. T stage was (cT2/3/4/unknown): 4/42/8/2. n=50 pts had cN+ disease. Main adverse events grades 3-4: leukopenia (17.9%), neutropenia (46.6%), and diarrhea (17.0%). All pts underwent tumor resections. R0 resection rate was 92.9%. Eight pts had anastomotic leakage. One postoperative death occurred. pCR was found in 12 pts (21.4%) and a further n=14 pts (25.0%) had near complete response. Median DFS was 42.5 months and the 3-year OS rate was 82.1%. The primary endpoint of achieving a pCR > 20% was reached. No unexpected safety issues were observed. Survival data are promising. This article is protected by copyright. All rights reserved.