Polypharmacy in Elderly Patients Receiving First-Line Treatment for Pancreatic Adenocarcinoma: Analysis of Potential Drug-Drug Interactions and Outcome.

Objectives

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality and mainly affects older adults, who frequently experience polypharmacy. While systemic therapy may improve outcomes in selected older patients, the use of multiple drugs increases the risk of potential drug-drug interactions (pDDIs). This study aimed to evaluate the prevalence and characteristics of pDDIs in older patients with PDAC receiving first-line systemic therapy and their potential impact on clinical outcomes.

Methods

We conducted a retrospective single-center study including patients aged ≥ 75 years with PDAC who initiated first-line systemic therapy between December 2011 and January 2023. Prescription data were retrieved from institutional and outpatient pharmacy databases, and all concomitant medications were recorded. pDDIs were assessed using Intercheck Web and classified as A (minor), B (moderate), C (major but manageable), or D (contraindicated). Patients (n = 140) were stratified according to the number of active pharmaceutical ingredients (APIs) at treatment initiation: <5 (n = 53), 5-20 (n = 43), and >20 (n = 44).

Results

A higher number of APIs was significantly associated with an increased burden of pDDIs, including A, B, C, and D interactions (all p < 0.001), with patients receiving >20 APIs showing the highest prevalence of clinically relevant interactions. Overall, 70% of patients had at least one pDDI, but no significant differences were observed in 1-year overall survival, access to second-line therapy, or chemotherapy type across API groups.

Conclusion

Polypharmacy significantly increases the risk of pDDIs in older patients with PDAC, but this did not translate into differences in 1-year survival or access to subsequent therapy.