Chemotherapy in pancreatic ductal adenocarcinoma: When cytoreduction is the aim. A systematic review and meta-analysis

• Published in: Cancer treatment reviews 2022-03, Vol.104, p.102338-102338, Article 102338
• Main Authors: Meneses-Medina, Monica I., Gervaso, Lorenzo, Cella, Chiara A., Pellicori, Stefania, Gandini, Sara, Sousa, Maria J., Fazio, Nicola
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - pathology; Albumins - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cytoreduction Surgical Procedures; Deoxycytidine - therapeutic use; Fluorouracil - therapeutic use; FOLFIRINOX; GEM-NAB; Humans; Leucovorin - therapeutic use; Meta-analysis; Paclitaxel - therapeutic use; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - etiology; Pancreatic Neoplasms - surgery; Prospective Studies; Retrospective Studies
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2022.102338

•In this meta-analysis of 40 studies, FOLFIRINOX and GEM-NAB showed similar RECIST-based overall response rate (ORR) (30% for each).•However, there was a statistically significant higher disease control rate with FOLFIRINOX (85%) than with GEM-NAB (80%).•Additionally, both regimens showed superior ORR for stage IV (36%) than stage II-III (25%). In pancreatic ductal adenocarcinoma cytoreduction can be curative, or palliative. FOLFIRINOX and GEM-NAB are the two FDA/EMA approved regimens for advanced disease. We aim to identified the most cytoreductive regimen on the basis of current literature. PUBMED was searched for studies published to April 2021. Abstracts of annual meetings ASCO 2009–2021, and ESMO 2015–2020, were searched as well. Phase II, phase III clinical trials, prospective, observational and retrospective studies, reporting overall response rate (complete + partial response) (ORR) in patients treated either with FOLFIRINOX or GEM-NAB were included. The meta-analysis was performed using a randomized-effects model. Main outcome was cytoreduction with each regimen reported as ORR according to RECIST. Among 2183 studies identified, 40 fulfilled the selection criteria (22 FOLFIRINOX, 18 GEM-NAB), totaling 2883 patients. Pooling of data found similar ORR between regimens: FOLFIRINOX [30% (95 CI 26–34%)] and GEM-NAB [30% (95 CI 26–35%),] P = 0.928. Disease control rate (DCR) was significantly higher with FOLFIRINOX [85% (95CI 82–88%)] compared to GEM-NAB [80% (95CI 77–84%)], P = 0.012. A significantly higher ORR irrespective of the regimen was observed in stage IV [36% (95CI 32–40%)] versus stage II-III [25% (95CI 20–31%)], P = 0.002. Our meta-analysis did not find significant superiority of one regimen over the other in terms of RECIST-based cytoreduction both in palliative and curative setting of patients with pancreatic adenocarcinoma. The significantly better DCR with FOLFIRINOX compared with GEM-NAB deserves further investigation including waterfall plot and correlations with potential predictive factors.