O93: Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection

Abstract

Abstract Background Repurposing existing drugs for use in oncology is more safe, efficient and cost-effective than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance and many of the hallmarks of cancer. This study aims to assess the impact of calcium channel blockers (CCB) in pancreatic cancer. Methods Retrospective population study including patients in the SEER-Medicare linked database who underwent resection with curative intent of pancreatic ductal adenocarcinoma diagnosed between 2007 and 2017. Adjusted cox regression models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, we assessed the impact of CCB separately in patients receiving chemotherapy. Results 6,223 patients were included, of whom 660 were prescribed CCB. 591 patients received neoadjuvant chemotherapy prior to resection; in this cohort CCB prescription was associated with a significant improvement in overall survival when adjusting for multiple prognostic factors (aHR=0.715, 0.514-0.996, P=0.047). This effect was not observed in patients who did not receive neoadjuvant chemotherapy (aHR=1.082, 0.982-1.191, P=0.112), or in the overall cohort (aHR=1.056, 0.963-1.158, P=0.248), suggesting a chemosensitising effect. Discussion CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy. This indicates a chemosensitising effect of CCB, which mirrors previous laboratory studies. This study defines those receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.