Inhibition Effect of Pancreatic Exocrine Insufficiency on Immune Checkpoint Inhibitor Treatment in Pancreatic Cancer: A Retrospective Study

Abstract

Introduction

Chemotherapy combined with immune checkpoint inhibitors (ChIM) is used to treat advanced pancreatic ductal adenocarcinoma (PDAC). However, the efficacy of ChIM is similar to that of chemotherapy alone.

Methods

To assess potential factors affecting the effectiveness of ChIM, we analyzed the clinical data of 359 patients with PDAC who visited the hospital during June 2017 to December 2022.

Results

Surgical resection, diabetes, and ChIM were risk factors for pancreatic exocrine insufficiency (PEI). The adjusted odds ratio of ChIM was 2.63 (95% confidence interval (CI) 1.492–4.626) (P = 0.001). The incidence of PEI in the ChIM group (76.9%) was significantly higher than that of the chemotherapy group (60.2%) (P = 0.004). Survival analysis showed that ChIM did not improve the survival rate of patients with PDAC (hazard ratio (HR) 0.92, 0.707–1.197) (P = 0.534) in comparison with that of the chemotherapy group. However, in patients without PEI, those receiving ChIM showed a higher 1-year overall survival (OS) rate of 70.8% (two-sided, P = 0.045) and a median OS of 22.0 months (95% CI 11.5–32.5). Moreover, pancreatic enzyme replacement therapy significantly improved the OS of patients with PDAC (HR = 0.73, 95% CI = 0.561–0.956) (P = 0.022).

Conclusion

Immune checkpoint inhibitors (ICIs) increased the incidence of PEI in patients with PDAC. The OS was not different between patients receiving chemotherapy and ChIM due to irregular PERT treatment. The finding show that pancreatic enzyme replacement therapy may improve the response rate of patients with PDAC to ICIs.

Keywords:

• pancreatic cancer
• pancreatic exocrine insufficiency
• immune checkpoint inhibitors
• pancreatic enzyme replacement therapy

Data Sharing Statement

All the data in this study are available upon request from the corresponding author.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (31671440) and Key Science and Technology Research Project of Henan Province (212102310151).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.