Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis of Individual Patient Data

Abstract

Introduction Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). The aim of this study was to assess the effectiveness of GEM-NAT on overall survival (OS) in resected and non-resected patients. Methods: A systematic review and meta-analysis of individual participant data (IPD) of all published articles on NAT for BR-PDAC was performed. The definition of BR was given according to NCCN preoperative radiological criteria. The primary outcome was OS. Secondary outcomes were disease-free survival (DFS), toxicity, drop out, resection rate and complete resection (R0). Finding: Six studies investigating GEM-NAT in BR-PDAC patients were included. Median OS was 22·9 - 41·2 and 9·3 - 15·4 months in resected and nonresected groups respectively. Four centers provided IPD of 170 patients who received GEM-NAT, with addition of radiotherapy in 108 (63%). 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. In the IPD cohort, resection and R0 rates were 62% and 88%, respectively. Interpretation: GEM-NAT may improve survival in BR-PDAC. Resected patients reached a significantly longer OS than non-resected. GEM-NAT results in good OS both in resected and non-resected patients with acceptable toxicity and perhaps fewer drop outs, as compared to other NAT regimens. Results from randomized controlled trials (RCTs) are awaited to validate these findings. Funding Statement: The authors declare: None. Declaration of Interests: The authors declare: No existing conflict of interest.