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

ABSTRACT

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE 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.