e16532 Background: Dipeptidyl peptidase-4 (DPP4) is a cell surface protein expressed in variable amounts on different tissues and plays a vital role in tumor biology as well as regulation of the immune system. In-vitro studies have shown that the DPP4 biochemical activity is twice as high in prostate cancer cells compared to benign prostate tissues. Furthermore, blocking of DPP4 activity in-vitro was demonstrated to inhibit tumor angiogenesis and tumor invasiveness through a number of cellular mechanisms. Meanwhile, DPP4 expression is modest in normal as well as cancerous pancreatic cells. Methods: Using linked SEER and MEDICARE database, we identified patients with prostate cancer (PRC) or pancreatic cancer (PC) with coexisting type II diabetes mellitus. Furthermore, we analyzed the impact of DPP4 inhibition in the overall survival (OS) in these patients between 2001 and 2013. Analyses were performed using SAS, version 9.4. We excluded patients taking metformin. Results: We identified 7229 patients with PRC and 2401 patients with PC. OS was significantly better in PRC patients taking DPP4 inhibitors (262 patients) with HR 0.75 (95% CI: 0.59-0.97; P = 0.02) compared to those not on DPP4 inhibitors. Meanwhile, for patients with PC, OS was not significantly different between patients taking DPP4 inhibitors (177 patients) compared to those who were not (HR 1.03; 95% CI: 0.88-1.21; P = 0.7). Subgroup analyses of PRC patients demonstrated a trend toward a beneficial effect of DPP4 inhibitors, irrespective of stage (stage I, NR; stage II, HR 0.81; stage III, NR; stage IV, 0.76),use of chemotherapy (HR 0.83 with chemotherapy and HR 0.70 without chemotherapy) or hormonal use (ADT) (HR 0.87 with ADT and HR 0.71 without ADT), prostatectomy (HR 0.50 with prostatectomy and HR 0.77 with no prostatectomy) or radiation (HR 0.89 with radiation and HR 0.64 without radiation). Conclusions: This is the first population-based analysis showing the OS benefit of DPP4 inhibitors in PRC patients. On the other hand, OS was not improved in PC patients taking DPP4 inhibitors likely due to low levels of expression of DPP4 cell surface protein on pancreatic tissues. A prospective trial would help confirm our findings.
