Oxaliplatin, 5FU and Nab-Paclitaxel As Neoadjuvant Regimen in Patients with Resectable Oesogastric Adenocarcinoma: A GERCOR Phase 2 Study (FOXAGAST).

4035 Background: Peri-operative chemotherapy is the standard of care in Resectable OesoGastric Adenocarcinoma (ROGA), with several validated regimens such as Cisplatin-5FU, FOLFOX, ECF/X, or FLOT. Nanoparticle-bound (Nab) paclitaxel is active in OGA. Tumor regression grade (TRG) is an objective parameter for assessing efficacy of neoadjuvant chemotherapy (NACT). The study objective was to evaluate TRG with Nab-paclitaxel combined with FOLFOX in ROGA patients (pts). Methods: HER2-negative ROGA pts over 18 yrs received Nab-paclitaxel (150mg/m2) and FOLFOX (oxaliplatin 85 mg/m2; 5FU 2400mg/m2 over 48h, and leucovorin 400mg/m2) on D1 q2w for 6 cycles in preoperative setting. 6 postoperative cycles were kept at investigator’s discretion. Primary endpoint was pathological complete response rate (TRG1) after NACT. According to Fleming design 49 pts had to be included to test H0 (10% TRG1) and H1 (25% TRG1) with unilateral α of 5% and ß of 10%. To reject H0, TRG1 had to be achieved in at least 8 pts. Results: 49 pts (36 male, median age 63.7 yrs, 53% N+) were included between 6/2015 and 3/2017. Median number of NACT cycles was 6 (range 3-6). Median dose-intensity was 96% (38-103), 97% (47-103) and 99% (50-112) for Nab-paclitaxel, oxaliplatin, and 5FU, respectively. Surgery could not be performed in 5 (10.2%) pts due to tumor progression or poor performance status. Tumor resection was R0 for 42/44 (95.5%) pts. Centrally blinded review classified tumors as TRG1 to TRG5 for 8 (16.3%), 11 (22.5%), 4 (8.2%), 18 (36.7%) and 3 (6.1%) pts, respectively. With a median follow-up of 14.2 m, 12 m-PFS was 88.4 % (95% CI: 74.2-95.0). Grade 3 or worse toxicities in NACT phase were non febrile neutropenia in 10 pts (20.4%), nausea in 4 (8.2%), diarrhea in 4 (8.2%) and neuropathy in 3 (6.1%). 14/44 (31.8%) pts experienced per or post-operative complications, including fistulas (5 pts), ischemic complications (4), infections (3), and anesthesia-related complications (2). 3/44 (6.8%) pts died from surgical complications. Conclusions: This regimen shows promising activity in ROGA with a high rate of TRG1/TRG2 responses. Toxicity is manageable but a high rate of surgical complications was observed. Clinical trial information: NCT02486601.