Preoperative treatment of potentially-resectable pancreatic adenocarcinoma with fixed-dose rate gemcitabine (GEM), bevacizumab (BEV), and 30 Gy radiotherapy (RT)

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4631 Background: Nearly 80% of patients with resected pancreatic cancer develop local or distant failure within two years. We hypothesized that short-course neoadjuvant treatment with systemically-active doses of combination chemotherapy and RT to the surgical margin may improve outcomes. Methods: This is a single center, two stage phase II trial of induction fixed-dose rate (FDR) GEM (1,500 mg/m2) plus BEV (10 mg/kg) q 2 weeks for three cycles, followed by BEV (10 mg/kg) with accelerated RT (30 Gy in 10 fractions) directed at the gross tumor volume and a 1–2 cm vascular margin. Eligible pts had FNA-proven pancreatic adenocarcinoma and were potentially-resectable on screening pancreas protocol CT scan. Stage I required six pts; 48 resected pts are required to evaluate dual primary endpoints: a 25% improvement in the margin-negative resection rate (65% to 80%) and a 10% pathological response rate (≥80% power; combined type I error 0.14). Results: This is an exploratory analysis of stage I data. Fourteen pts completed treatment: 10 males; median Karnofsky score 90; and median age 57 (37–75). Lesions measured 1.6–4.5 cm with CT criteria for portal venous invasion (n=5) and malignant adenopathy (nodes ≥ 1 cm; n=6). Median treatment duration was 56 days (55–71 days) with three delays. Only one of six pts experienced treatment-related grade 3 toxicity, while two pts required dose reduction due to grade 2 events. Median Ca 19–9 decreased from 128 to 32 U/ml. Radiographic responses included 1 CR, 2 PR, and 10 SD upon completion. Ten pts underwent pancreatoduodenectomy with two portal vein resections. Eight of ten pts had negative surgical margins (80%) with three (30%) near-complete pathological responses (microscopic foci of residual tumor only). Four pts (4/14) had metastatic disease; all had nodes ≥ 1 cm on pretreatment CT (p<0.02). Median length of stay was 10 days (2–17). Four pts had grade 3 wound complications (29%) with one grade 2 pancreatic leak (10%). Conclusions: Induction therapy with FDR GEM and BEV, followed by concurrent BEV/RT to 30 Gy, is safe neoadjuvant treatment for patients with resectable pancreatic cancer. The resectability rate and evidence for pathologic downstaging meet criteria for accrual to stage II. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech