Clinical Impact of Nonselective Beta-Blockers on Survival in Patients with Pancreatic Cancer- Revival of Well Known Drugs?

Background: In preclinical animal studies it has been shown that l stress stimulates PDAC growth and increases catecholamines, VEGF and NGF. Here the impact of beta-blockers in resected PDAC patients was investigated. Methods: PDAC patients from two European centers between 2002 and 2012 (n=595) were studied. 159 patients received beta-blockers (BB). 17 patients with non-selective BB (NSBB) were compared to 85 receiving no BB (NBB) using a matched-pair analysis. 142 patients with beta1 selective agents (SB1B) were also analyzed. Univariate and multivariate survival analysis (Cox) was performed. Organoids from PDAC specimen were treated with B1SB, B2SB, NSBB and GEM. Results: Median age of patients was 70 y (22-88 y). Patients with any BB, had median OS of 25 mo vs. 21 mo with NBB (p=0.0084). Median OS of NSBB was 40 mo vs. 23 mo for NBB (p=0.0007) and 21 mo for SB1B (p=0.0396). Hypertension (HPT) was associated with lower OS compared to no HPT. Even among patients with HPT, a longer median OS was observed among NSBB compared to NBB (40 vs 19 mo; p=0.041). Organoids showed fewer RLU when treated with NSBB or SB2B in addition to GEM comapred to GEM alone (p=0.032). SB1B did not reveal any difference. Conclusion: For the first time a matched pair analysis comparing NSBB to SB1B and NBB in PDAC patients is presented. NSBB almost doubled the OS in PDAC patients in an adjuvant setting. SB1B did show little differences regarding OS. Taken together, targeting the adrenergic beta2-pathway might be a therapeutic strategy.