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2015 ; 21
(11
): 2471-9
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Angiotensin system inhibitors and survival outcomes in patients with metastatic
renal cell carcinoma
#MMPMID25724518
McKay RR
; Rodriguez GE
; Lin X
; Kaymakcalan MD
; Hamnvik OP
; Sabbisetti VS
; Bhatt RS
; Simantov R
; Choueiri TK
Clin Cancer Res
2015[Jun]; 21
(11
): 2471-9
PMID25724518
show ga
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 IFN?. 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.
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