A multicenter, phase II trial of preoperative gemcitabine and nab-paclitaxel for resectable pancreas cancer: The AGITG GAP study.

Abstract

Background: Recent pancreatic cancer (PC) series show 41% (95%CI 40-43%) of patients (pts) achieve an R0 resection (margin clearance 1mm). In neoadjuvant chemotherapy trials for resectable PC, only 54-89% undergo pancreatic resection with R0 rates of 74- 80%. Nab-paclitaxel(nab-pacli) and gemcitabine(GEM) chemotherapy(CX) is an active regimen in metastatic disease. We aimed to determine feasibility and R0 resection rate of 85% with peri-operative nab-pacli and GEM for resectable PC. Method(s): Pts with operable PC received 2 cycles of neo-adjuvant nab-pacli 125mg/m2 followed by GEM 1000mg/m2CX on days(D) 1, 8 and 15(28D cycle) followed by resection and then post- operative CX(4 cycles). Result(s): Forty-one pts were enrolled (2012-14). Median age = 65 (range 43-79), 41% male. Thirty-six (88%) pts underwent surgery, while five (12%) did not (2 disease progression, 2 refused surgery, 1 cholangitis). Only 4/36 (10%) had grade septic events, no grade pancreatic leak, and no treatment related deaths. Thirty pts had pancreatic resection (73%; 29 had evaluable cancer and 15/29 (52%) had grade 0-2 tumour regression; one did not have cancer on central pathology review). Six (15%) pts had unresectable disease at surgery. Pre-operative nab-pacli and GEM produced an R0 rate of 52% (15/29; 95%CI 34-69%) with a minimum 1mm margin and an R0 rate of 86% (25/29; 95%CI 68-96%) with a 0mm margin. 39/41 (95%) completed planned induction CX (although dose modifications/omission were required - mostly omission of D15). Post- operatively, eighteen pts (18/30, 60%) commenced CX, with 14/18 (78%) completing all 4 cycles of planned CX; whilst four pts commenced chemoradiation, but 2 withdrew due to disease progression. Conclusion(s): Pre-operative nab-pacli and GEM was delivered safely and achieved an R0 resection rate clinically significantly higher than the mean of surgical series using similar pathology criteria. Our pre-operative regimen was delivered to 95% of patients, but in contrast post-operative CX was less achievable with only 60% commencing treatment. Neoadjuvant nab-pacli and GEM is an encouraging strategy to improve outcomes in resectable PC and merits testing in a randomised setting.