SWOG S1505: Initial findings on eligibility and neoadjuvant chemotherapy experience with mfolfirinox versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma.

Abstract

414 Background: Clinical outcomes after curative therapy of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. For early control of systemic disease with aggressive perioperative chemotherapy (CTx), we conducted a prospective trial in the National Clinical Trials Network (NCTN) setting. Methods: S1505 was a randomized phase II trial of periop (12 weeks pre-, 12 weeks post-op) CTx with either mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin – without bolus 5-FU and leucovorin; Arm 1), or gemcitabine/nab-paclitaxel (Arm 2). Eligibility required adult patients with ECOG PS 0 or 1, confirmed tissue diagnosis of PDA, and resectable disease: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Primary outcome is 2-year overall survival (OS), using a “pick the winner” design; for 100 eligible patients, accrual up to 150 patients was planned, to account for cases deemed ineligible at central radiology review. Results: From 2015 to 2018, 147 patients were enrolled; 74 to Arm 1; 73 to Arm 2. At central radiology review, 42/147 (29%) were ineligible; of these, 15 (36%) had venous involvement ≥ 180°, 22 (52%) had arterial involvement, 28 (67%) had distant disease. One patient had distal cholangiocarcinoma (ineligible); one withdrew consent after randomization. Eligible patients (n = 103) had median age 64 years; males 58%; whites 89%; PS 0 64%. Of 103, 99 (96%) started and 86 (83%) completed preop CTx. There was one death due to sepsis and 61 additional patients experienced grade 3/4 toxicities. To date, 76 of 99 (77%) patients went to surgery and 72 (73%) underwent resection. Conclusions: This is the first-ever NCTN study of periop CTx for resectable PDA. Accrual was brisk, establishing feasibility. Ineligible cases after central radiology review highlight quality control and physician education imperatives for neoadjuvant PDA trials. Preop CTx safety and resection rates are encouraging. Follow up for OS is ongoing. Clinical trial information: NCT02562716.