Angiotensin Inhibitors as Treatment of Sunitinib/Pazopanib-induced Hypertension in Metastatic Renal Cell Carcinoma

Abstract

Previous preclinical research suggests that angiotensin system inhibitors may have a direct anti-angiogenic effect that may be synergistic with the currently available angiogenesis inhibitors. In this retrospective study, we reviewed 303 patients with metastatic renal cell carcinoma treated with first-line angiogenesis inhibitors. Our results demonstrate a longer overall and progression-free survival for angiotensin system inhibitor users among patients with treatment-related hypertension. If validated, these results may guide the choice of antihypertensive medication among patients being treated with angiogenesis inhibitors. Background: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). Patients and Methods: We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for known risk factors. Results: Progression-free survival (PFS) and overall survival (OS) were similar among patients with baseline HTN (n = 197; 65%) versus patients with no baseline HTN (n = 106; 35%) (PFS; P = .72) (OS; P = .54). There was a significant difference between patients with treatment-induced HTN (n = 110) versus patients with no treatment-induced HTN (n = 193) for PFS (15.6 vs. 6.4 months, respectively; P <.001) and OS (34.9 vs. 13.9 months, respectively; P <.001). Use of ASIs at baseline (n = 126; 41.6%) had no impact on outcome as compared with patients receiving other antihypertensive medication (n = 71; 23.4%) or with patients with no baseline antihypertensive medication (n = 106; 35.0%). Among patients with TKI-induced HTN (n = 110), however, ASI users (n = 91) demonstrated improved OS (37.5 vs. 18.1 months; P = .001) and PFS (17.1 vs. 7.2 months; P = .004) versus ASI nonusers (n = 19), respectively. Conclusion: Our results demonstrate survival benefit for ASI users among patients with TKI-induced HTN. These results, however, require further validation in a prospective setting. (C) 2016 Elsevier Inc. All rights reserved.