Multicenter phase 2: Capecitabine (CAP) + oxaliplatin (OX) + bevacizumab (BEV) + trastuzumab (TRAS) for patients (pts) with metastatic esophagogastric cancer (MEGCA).

4038 Background: In MEGCA, cisplatin+CAP has RR 46% and OS 12.1 mos with BEV (AVAGAST) and RR 47% and OS 13.8 mos with TRAS (ToGA). We sought to improve these results by combining CAPOX with both BEV and TRAS. Methods: Pts with HER2/neu IHC 3+ or FISH+ MEGCA, with 0-1 prior chemo, received a loading dose of TRAS 4mg/kg, day (d) 1. One week later, pts received BEV 7.5mg/kg/d1, TRAS 6mg/kg/d1, OX 130mg/m2/d1 and then q21d. CAP d1-14/q21d was decreased from 1700mg/m2/d to 1200mg/m2/d after 4 of the first 5pts developed G3 diarrhea. Consenting pts underwent identical research biopsies prior to and 7 days after TRAS loading dose. Primary endpoint was RR by RECIST 1.1, scored by independent Harvard Tumor Imaging Metrics Core. Results: Of 35 pts enrolled, median age 58 (32-80), 4F/31M, HER2/neu IHC3+: 25/FISH+: 10, ECOG PS 0: 18/ 1: 17, prior chemo 10, primary: esophagus 16/GEJ 10/gastric 9, sites of mets: LN 26, liver 19, lungs 9, bone 2, other 6. Pts have received mean 16 cycles (2-50+). Of 34 pts (1 too early...