Impact of DPP4 Inhibition on Survival in Patients With Metastatic Renal Cell Carcinoma and Type 2 Diabetes Mellitus

Background: Dipeptidyl peptidase IV (DPP4) is a cell surface receptor that possesses numerous substrates implicated in tumor growth and metastasis. Prior studies have suggested an association between DPP4 inhibition and increased progression-free survival (PFS) and overall survival (OS) in colorectal and lung cancers but no benefit in breast or pancreatic cancers. However, no studies to date have explored the impact of DPP4 inhibitors (DPP4i) in patients with metastatic renal cell carcinoma (mRCC). In this study we present a first-time analysis examining the impact of DPP4i use on PFS and OS in patients with mRCC and type 2 diabetes mellitus.

Methods: We performed a retrospective analysis of patients with diabetes and mRCC at the University of Virginia. The study group comprised those whose diabetic regimen included a DPP4i during mRCC treatment. The control group comprised patients whose diabetic regimen did not include a DPP4i during treatment. Cox regression analysis was utilized to determine the hazard ratios of progression and death between groups.

Results: Fifty-nine patients were eligible for the study, with 11 in the DPP4i group and 48 in the control group. Cancer progression occurred in 81.8% of patients in the DPP4i group and 66.7% in the control group. No statistically significant differences on PFS (HR: 1.60 [95% CI, 0.75-3.43]) or OS (HR: 0.69 [95% CI, 0.28-1.70]) were found between groups.

Conclusions: This retrospective study explored the effect of DPP4i on outcomes in patients with mRCC and diabetes. DPP4i have been shown to have favorable effects on PFS and OS in some cancers but not in others. The results of this study suggest that DPP4i do not confer clinical benefit in patients with mRCC. Larger studies are warranted to better elucidate the effect of DPP4i in mRCC and the mechanisms underlying differential tumor response to these agents in different malignancies.