Phase II trial of bevacizumab, gemcitabine, oxaliplatin in patients with metastatic pancreatic adenocarcinoma

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4553 Background: The combinations of gemcitabine and oxaliplatin (GemOx) and bevacizumab and gemcitabine have activity in pancreatic cancer. Based on these observations, the NCCTG initiated a multicenter phase II study to evaluate the combination of an active cytotoxic doublet and a targeted agent to determine whether improvement in 6-month survival in previously untreated patients with metastatic pancreas cancer could be achieved. Methods: Treatment consists of gemcitabine 1000 mg/m2 IV over 100 minutes and bevacizumab 10 mg/kg IV given on day 1, 15; oxaliplatin 100 mg/m2 IV is given on day 2, 16, repeated every 28 days. Eligibility includes: no prior chemotherapy, ECOG PS 0–2, bili< 2x UNL, AST< 5x UNL. Pts with stable full dose anticoagulation are eligible. Bevacizumab specific exclusions include no recent stroke, heart attack, embolus, tumor invasion or significant proteinuria. CT scans are obtained every 2 cycles. Treatment continues until disease progression, severe adverse events (AEs), or patient refusal. Results: Eighty-two patients were enrolled from 7/05 to 2/06. Median age was 63 (range: 32 - 86). 24 of 82 (29%) evaluable pts had a maximum grade ≥ 4 AE (at least possibly related to treatment). Grade 4 events included (% of pts): neutropenia (7%), thrombosis (6%), thrombocytopenia (5%), pneumonitis (2%), ischemia-cerebral (1%), abdominal infection (1%), small intestine perforation (1%), and small bowel leak (1%). Three patients died from grade 5 events (1-gastric perforation, 1-cerebral ischemia, 1-multi-organ failure). 80 patients were evaluable for outcome assessment (excludes 2 ineligible cases). Median follow-up was 10.3 months (range: 6.3 - 14.7) in the 19 patients still alive. 6-month survival was 65.0% (95% CI: 53.5% - 75.3%). Median survival was 8.1 months (95% CI: 6.5 - 9.3) and median TTP was 5.7 months (95% CI: 4.4 - 6.4). The confirmed response rate was 11.3% (95% CI: 5.3 - 20.3%) with 1 complete and 8 partial responses. Conclusions: In this multi-centered, cooperative group study, promising efficacy with this three-drug combination was observed especially in regards to six- month and median survival. The observed adverse events are comparable to historical controls although caution should be exercised in light of the three grade 5 events. [Table: see text]