Background: Response on FDG-PET scan during preoperative chemotherapy has prognostic significance. PET non-responders do poorly whether they continue the same chemotherapy or proceed directly to surgery [JCO 24: 4692; 2006, Lancet Onc 8:797;2007) Early identification of treatment failure using PET scan may spare patients (pts) from inactive therapy and allow for cross-over to alternative therapies. We performed a phase II trial to examine the effectiveness of FDG-PET directed early switching to salvage chemotherapy measured by 2 year disease free survival (DFS) in the PET non-responding group. Methods: Pts with PET avid, EUS and laparoscopically staged T3 or Node positive resectable gastric or GEJ adenocarcinoma received induction with epirubicin 50mg/m2, cisplatin 60mg/m2, capecitabine 625mg/m2 bid days 2-21(ECX) and bevacizumab 15mg/kg day 1. PET scan was repeated at week 3. PET responders (≥35% decline in SUV) continued ECX for 2 more cycles. PET non-responders switched to 2 cycles of salvage therapy: docetaxel 30mg/m2 d1, d8 q21 days, irinotecan 50mg/m2 d1, d8 q21 days and bevacizumab 15mg/kg day 1. Pts had surgery 4 weeks after cycle 3. Results: 20 of planned 60 pts were enrolled before the study closed for poor accrual. 14 male (64%), 8 female (39%), median age 62, median KPS 90. 11(55%) had a PET response after the first cycle. 10/11 (91%) underwent R0 resection: 1/10 pathologic CR, 3/10 pathologic PR. 9/20 PET non-responders switched to the salvage regimen. 7/9 Non-responders had R0 resection, none achieved a pathological response. The DFS for PET responders was 27.8mos (95% CI 10.3-27.8) and DFS in salvage group has not been reached. There was no significant difference in DFS between the two groups (p= 0.4). Follow up for overall survival is ongoing. Biologic correlative studies are pending. Conclusions: Response on PET scan during induction chemotherapy can identify early treatment failures. The results for therapy cross-over indicate a potentially improved DFS with salvage chemotherapy. Results from this trial are hypothesis generating and merit evaluation in a larger clinical trial. Supported by a grant from Genentech. Clinical trial information: NCT00737438.