Angiotensin system inhibitor use improved overall survival compared with other antihypertensive agents (HR 0.838; P=0.0105; 26.68 vs 18.07 months) in patients with metastatic renal cell carcinoma.
Cohort (n=4,736)
Does angiotensin system inhibitor use improve overall survival in patients with metastatic renal cell carcinoma?
Angiotensin system inhibitor use is associated with improved overall survival in patients with metastatic renal cell carcinoma receiving VEGF-targeted therapy.
Effect estimate: HR 0.838
Absolute Event Rate: 26.68% vs 18.07%
p-value: p=0.0105
PURPOSE: The renin-angiotensin system may play a role in carcinogenesis. The purpose of this study was to evaluate the impact of angiotensin system inhibitors (ASI) on outcomes in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era. EXPERIMENTAL DESIGN: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. RESULTS: A total of 4,736 patients were included, of whom 1,487 received ASIs and 783 received other antihypertensive agents. Overall, ASI users demonstrated improved overall survival (OS) compared with users of other antihypertensive agents (adjusted HR, 0.838, P = 0.0105, 26.68 vs. 18.07 months) and individuals receiving no antihypertensive therapy (adjusted HR, 0.810, P = 0.0026, 26.68 vs. 16.72 months). When stratified by therapy type, a benefit in OS was demonstrated in ASI users compared with nonusers in individuals receiving VEGF therapy (adjusted HR, 0.737, P < 0.0001, 31.12 vs. 21.94 months) but not temsirolimus or IFNα. An in vitro cell viability assay demonstrated that sunitinib in combination with an ASI significantly decreased RCC cell viability compared with control at physiologically relevant doses. This effect was not observed with either agent alone or with other non-ASI antihypertensives or temsirolimus. CONCLUSIONS: In the largest analysis to date, we demonstrate that ASI use improved survival in mRCC patients treated in the targeted therapy era. Further studies are warranted to investigate the mechanism underlying this interaction and verify our observations to inform clinical practice.
McKay et al. (Sat,) conducted a cohort in Metastatic Renal Cell Carcinoma (mRCC) (n=4,736). Angiotensin system inhibitors (ASI) vs. Other antihypertensive agents or no antihypertensive therapy was evaluated on Overall survival (OS) (HR 0.838, p=0.0105). Angiotensin system inhibitor use improved overall survival compared with other antihypertensive agents (HR 0.838; P=0.0105; 26.68 vs 18.07 months) in patients with metastatic renal cell carcinoma.