Efficacy, safety, and quality-of-life improvement of chemotherapy regimens for treatment of unresectable pancreatic cancer: a systematic review and network meta-analysis of phase III randomised controlled trials

Authors: Ezeh, E.T., Welton, N.J., Primrose, J., Hickish, T., Porter, S., Scammell, J., Jiang, N.

Journal: Heliyon

Publication Date: 01/09/2026

Volume: 12

Issue: 14

eISSN: 2405-8440

DOI: 10.1016/j.heliyon.2026.e45191

Abstract:

Background Patients with advanced pancreatic cancer (APC) are offered chemotherapy to improve their survival and quality of life. Comprehensive reviews of randomised controlled trials (RCTs) are necessary for decision-making about the treatment of APC. Objective This paper aimed to review and compare the efficacy, safety, and quality-of-life (QOL) outcomes of first-line chemotherapy regimens for APC treatment. Methods A systematic review followed by a network meta-analysis was performed to compare available evidence from phase III RCTs of chemotherapy regimens for APC from 1997 to 2021. The associated hazard and odds ratios with 95% confidence intervals, and surface under the cumulative ranking score were evaluated. Results Forty-four RCTs involving 16,836 patients, and comparing 47 regimens, were eligible for review. FOLFIRINOX achieved the best overall survival improvement. However, the best response rate was attained by pegvorhyaluronidase alfa combined with nab-paclitaxel plus gemcitabine. Diarrhoea, nausea and fatigue were the common adverse events reported in the RCTs. Single-agent gemcitabine (GEM) demonstrated mild toxicity compared to other regimens. Most regimens were associated with improved pain management, emotional well-being, global health status, appetite, and reduced constipation. However, mixed responses were observed for other QOL outcomes. Conclusions Combination therapies are associated with high toxicity profiles despite their improved survival outcomes. Therefore, more effective regimens are advocated, especially for those patients with poor performance status. Furthermore, inconsistent QOL information in RCTs could hinder meaningful comparison and integration of results across studies.

Source: Scopus