Gemcitabine-based neoadjuvant treatment in borderline resectable pancreatic ductal adenocarcinoma: a systematic review and meta-analysis of individual patient data

Abstract

Introduction: Several non-randomized studies investigated gemcitabine-based neo-adjuvant therapies (NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). The aim of this study was to assess the effectiveness of NAT on overall survival (OS) in resected and non-resected patients. Methods: A systematic review of all published articles on NAT for BR-PDAC was performed. The definition of borderline resectable was according to NCCN (v2.2016). A meta-analysis of individual participant data (IPD) was performed. Patients were divided in two groups: resected and non-resected. The primary outcome was OS. Secondary outcomes were disease-free survival (DFS), toxicity, resection rate and complete resection (R0). Results: Seven studies were included. Median OS was 22.9 - 41.2 and 9.3 - 15.4 months in resected and non-resected groups, respectively. Four centers provided IDP of 170 (68%) patients: all received gemcitabine-based neoadjuvant chemotherapy with additional radiotherapy in 121 (71%). Pooled median patient-level OS was 27.2 (95%CI 23 - 31.3) and 20.4 (95%CI 12.7 - 28) months in resected and non-resected groups (p=0.03). There was no significant difference in OS in patients treated with different protocols. DFS after resection was 17.9 (95%CI 14.3 - 21.5) months. Eighty-two (48.2%) patients experienced Grade III-IV toxicity. Resection and R0 rates were 62% and 88%, respectively. Conclusion: Gemcitabine-based NAT is effective in patients with BR-PDAC. Resected patients reached a significantly longer OS than non-resected. Compared to upfront surgery, NAT may achieve longer median OS both in resected and non-resected patients. Treatment sequencing and specific elements of NAT should be further investigated with RCTs.