ASCO GU 2021: A Multicenter Retrospective Analysis Examining The Effect Of Dipeptidyl Protease 4 Inhibitors On Progression-Free Survival In Patients With Prostate Cancer

( Targeted therapies often rely on cell surface protein expression.  One such potential target is dipeptidyl peptidase IV (DPP4), a cell surface protein also known as CD26 which expressed on a variety of cell types and with tumor- and tissue-dependent roles in cancer.  It has been reported that patients treated with inhibitors of DPP4, from the field of diabetic treatments, had longer PFS in colorectal cancers.  Consequently, the authors here investigated retrospective data to determine the effect of DPP4 inhibitors of PFS in diabetic patients with advanced (stage III/IV) prostate cancer. All subjects were on anti-hyperglycemic therapies and had received surgery, radiation, or both for prostate cancer.  Comparisons were drawn between subjects receiving a sulfonylurea (n=120) and those receiving a DPP4 inhibitor (n=41).

No significant difference was found in progression-free survival (PFS) between the two groups, with 59% (24/41) in the study population and 61% (73/120) in the control population have progressed (HR 1.01, 95% CI 0.64-1.61).  The median time to progression was not different (DPP 3.3 years, sulfonylurea (3.5 years).  As a subgroup analysis, the use of DPP4 inhibitor was associated with improved PFS after radiotherapy (4.7 v 2.7 years, HR 0.56, 95% CI 0.37-0.84, p = 0.0006).


The authors conclude that these data are contrary to those reported in other cancers: exposure to DPP4 inhibitors did not improve PFS in men with advanced prostate cancer.  They speculate that DPP4 may operate as a suppressor of AR signaling, and, thus, could have a role in altering the development of castration resistance.  Further analyses are planned, including in larger cohorts, and isolating the variable of hormone sensitivity.

Presented by: Kelsey Pan, MD MPH, Division of Hematology and Oncology, Department of Internal Medicine, University of Florida, Gainsville, Florida

Written by: Jones Nauseef MD, PhD. Fellow, Division of Hematology and Oncology, Weill Cornell Medicine/New York-Presbyterian Hospital. Twitter: @DrJonesNauseef during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021