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. 2019 Nov 7;11(11):1746.
doi: 10.3390/cancers11111746.

Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Kun-I Lin  1   2 , Jia-Lian Yang  3 , Yu-Chao Lin  4   5 , Che-Yi Chou  6   7 , Jin-Hua Chen  8 , Chin-Chuan Hung  3   9
Affiliations

Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Kun-I Lin et al. Cancers (Basel). .

Abstract

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

Keywords: advanced pancreatic cancer; adverse effects; chemotherapy; efficacy outcomes; target therapy.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results of the study.

Figures

Figure 1
Figure 1
PRISMA flow diagram of randomized controlled trials included and excluded.
Figure 2
Figure 2
Pairwise comparisons of toxicities: experimental therapy vs. gemcitabine alone. Data presented as odds ratio (OR) with 95% confidence interval (CI); the 95% confidence interval that did not contain the value of 1 represents as statistical significance. PLA: doublet platinum-based treatment; GEM: gemcitabine; F: fluoropyrimidine only; F-based: fluoropyrimidine-based treatment; EGFRI: epidermal growth factor receptor inhibitor; ANGI: angiogenesis inhibitor; IMT: immunotherapy; TKI: tyrosine kinase inhibitor.
Figure 3
Figure 3
P-scores ranking plot. P-scores ranking plot represented the overall survival and the progression-free survival of interventions for advanced-staged pancreatic cancer. Treatment with best efficacy should be in the right-upper corner of the graph. PLA: doublet platinum-based treatment; GEM: gemcitabine; F: fluoropyrimidine only; F-based: fluoropyrimidine-based treatment; EGFRI: epidermal growth factor receptor inhibitor; ANGI: angiogenesis inhibitor; IMT: immunotherapy; TKI: tyrosine kinase inhibitor.
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