Phase II trial of fixed-dose rate gemcitabine, bevacizumab, and concurrent 30 gy radiotherapy as preoperative treatment for potentially resectable pancreatic adenocarcinoma.

Abstract

258 Background: Effective multimodality treatment for localized pancreatic cancer is elusive. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with short-course radiotherapy (RT) and the angiogenesis inhibitor bevacizumab (BEV) would improve margin negative surgical outcomes and complete pathological response rates. Methods: Multisite phase II trial evaluating all potentially-resectable pancreatic adenocarcinoma without major arterial involvement or portal venous occlusion. Dual primary endpoints included complete pathological response and margin negative resection rates of 10% and 80%. Subjects received FDR GEM on days 1, 15, and 29 combined with BEV (10 mg/kg IV), followed on day 43 by BEV and concurrent 30 Gy RT (3 Gy/fraction) over 10 days. After restaging, subjects underwent laparoscopy and possible resection after day 85. Stopping criteria required continuous monitoring of serious wound complications. Results: 58 subjects enrolled, of which 29 (50%) had suspected venous involvement. 57 completed treatment without dose-limiting toxicity or delays in surgery. Two grade 4 (3.4%) and 17 grade 3 toxicities (28.8%) occurred. Four patients progressed before surgery. 54 subjects underwent laparoscopy; ten had unexpected carcinomatosis, and one was unresectable. 43 subjects were resected (74%; 33 pancreatico-duodenectomy, 8 distal pancreatectomy, 1 total pancreatectomy, 1 Appleby); 19 (44%) required portal vein resection. Margin negative outcome was achieved in 38 (88%, 95% CI: 75%-96%) with one complete pathological response (2.3%; 95% CI: 0.1%- 12%) and seven (6 grade 3; 1 grade 4) wound complications (13%). Median overall survival (OS) was 16.3 months (95% CI: 13.9 -22.1) and 21.3 months (95% CI: 15.0-32.9) after resection. Median progression-free survival (PFS) was 5.7 months (95% CI: 3.9-9.1) and 9.9 months (95% CI: 5.7 to 14.1) after resection, with 7 local and 21 distant recurrences. Conclusions: Combination therapy was well-tolerated and was within statistical design parameters for the primary endpoints despite a significant proportion of borderline tumors.