Randomized phase 2 trial of peri- or post-operative chemotherapy in resectable pancreatic adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) has a remarkable trend to metastasize early. Accordingly, there is a strong rational to investigate preoperative chemotherapy in patients with resectable disease. We conducted a multicenter randomized phase 2 trial (PACT‐15; NCT01150630) to assess the role of combination chemotherapy in perioperative setting. Methods: Treatment‐naïve patients with 18‐75 yr, KPS>60 pathologically confirmed stage 1‐2 resectable PDAC were randomized to surgery followed by 6 cycles of adjuvant gemcitabine 1000 mg/m21,8,15q4w (arm A), or PEXG (cisplatin 30 mg/m2, epirubicin 30 mg/m2, and gemcitabine 800 mg/m2 1,15q4w and capecitabine 1250 mg/m2/day 1‐ 28) (arm B), or to 3 cycles of PEXG before and 3 after surgery (arm C). The primary endpoint was 1 year event‐free survival (EFS); the secondary endpoints were EFS, overall survival (OS), and the difference in pathological findings between arm A+B and arm C. With 24 eligible patients in each group (H0 20%; H1 40%; a 10%; b 20%) ≤16 events of 24 would support further evaluation of experimental therapy. Results: Between September 2010 and April 2015, 88 eligible patients were randomized in 9 Italian centers (arm A: 26, B: 30, C: 32). Basal patients and tumor characteristics are reported in the first table. Failure was observed (A/B/C) in 22/23/21 patients; 1‐year EFS was 6/26 (23%); 15/30 (50%); 21/32 (66%). Median EFS was 4.9; 12.4; 18.9 months (A vs C p=0.002). 19/22/18 (A/B/C) patients died; 3‐year OS was 35%/42%/55%. Median OS was 20.5, 25.1, not reached at 33 months (A vs C p=0.022). Pathological results are summarized in the second table. Main G3‐4 toxicity (A/B/C) was: neutrophils 23/38/54%; fatigue 4/7/6%; anemia 0/10/21%; vomiting 0/0/6%. Conclusions: Patients receiving perioperative chemotherapy had significant improvement of EFS and OS as compared to those receiving adjuvant treatment. This trial provides the strongest piece of evidence currently available in favor of preoperative chemotherapy in resectable PDAC. (Table Presented).