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World J Clin Oncol. Sep 24, 2021; 12(9): 787-799
Published online Sep 24, 2021. doi: 10.5306/wjco.v12.i9.787
Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer
Hakon Blomstrand, Atul Batra, Winson Y Cheung, Nils Oskar Elander
Hakon Blomstrand, Nils Oskar Elander, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
Atul Batra, Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India
Winson Y Cheung, Department of Oncology, University of Calgary, Calgary T2N 4N1, Canada
Author contributions: Blomstrand H, Cheung WY and Elander NO planned the study; Blomstrand H and Batra A performed the literature search; Blomstrand H, Batra A, Cheung WY and Elander NO assessed and interpreted the search results, and all were major contributors to the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they do not have any conflicting interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nils Oskar Elander, MD, PhD, Doctor, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden. nils.elander@liu.se
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: April 27, 2021
Revised: May 9, 2021
Accepted: August 12, 2021
Article in press: August 12, 2021
Published online: September 24, 2021
Abstract

In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.

Keywords: Pancreatic cancer, Palliative therapy, Cancer chemotherapy, Gemcitabine, Paclitaxel, nano albumin-bound, Folfirinox

Core Tip: This review summarizes and interprets published real-world evidence of the effectiveness and safety of treatment strategies in advanced pancreatic cancer. The real-world outcomes of first-line chemotherapy regimens such as folfirinox and gemcitabine/ nab-paclitaxel are thoroughly reviewed. The results of randomized controlled trials (RCTs) exploring the regimens seem to be largely generalizable in a real-world context. On second-line options, i.e. salvage chemotherapy following failure of first-line therapy, significant uncertainties remain. Additional RCTs and real-world evidence studies addressing current and novel regimens, and the optimal sequence of these, are needed.