Angiotensin System Inhibitors Extend Survival in Patients With Metastatic Renal Cell Carcinoma

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Use of angiotensin system inhibitors (ASIs) improved survival in patients with renal cell carcinoma (RCC) by 9 months compared with patients not taking any of these agents, according to a retrospective pooled analysis of a number of clinical trials presented at the symposium and discussed at a premeeting press cast. Survival was further improved if patients were also taking vascular endothelial growth factor (VEGF) receptor–targeted agents. These data are intriguing and need confirmation in a larger prospective study, stated the authors.

“Based on results of this study, an ASI should be considered for patients with metastatic RCC who require antihypertensive therapy and have no contraindications that preclude their use, especially patients receiving VEGF-targeted treatments. However, it is too early to determine if ASIs should be used for patients with metastatic RCC who do not have coexisting hypertension or another medical condition to warrant ASI treatment,” stated lead author Rana McKay, MD, clinical oncology fellow at Dana-Farber Cancer Institute, Boston, MA.

VEGF is an established target in metastatic RCC, she continued. ASIs include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These 2 classes of drugs act on the renin-angiotensin system and are used singly and in combination to treat hypertension as well as other medical conditions. Recent research suggests that the peptide hormone angiotensin II modulates VEGF-depending angiogenesis.

The study – the largest retrospective study to date evaluating the role of ASIs on outcomes in cancer patients – was based on a database of 4736 patients with metastatic RCC participating in phase 2 and phase 3 Pfizer-sponsored clinical trials conducted between 2003 and 2013. ASI use was defined as taking an ASI at baseline or within 30 days of cancer treatment initiation. Baseline hypertension was present in 48% of all patients; 1487 patients were taking an ASI, and 783 were taking other antihypertensive agents.

RCC treatments included VEGF-targeted agents such as sunitinib, sorafenib, axitinib, and bevacizumab, an mTOR inhibitor (temsirolimus), and interferon.

Overall survival (OS) for patients on ASI treatment was 26.68 months versus 17 months for non-ASI users (hazard ratio [HR] 1.213; P<.0009). In patients taking VEGF agents for metastatic RCC, ASI use significantly prolonged OS: 31 months for ASI users versus 21.94 months for nonusers (HR 1.38; P=.0003).

Moreover, tumor shrinkage was more likely in patients on ASIs. Median progression-free survival was 8.3 months for ASI users versus 6.5 months for nonusers (P=.0042).

A subgroup analysis of type of anticancer therapy showed that only concomitant VEGF and ASI use was associated with a significant survival benefit that persisted in a multivariate analysis adjusted for a number of cofactors, including age, gender, type of metastatic RCC therapy, presence of bone metastases, and risk groups. This association was not seen with mTOR inhibitors or interferon.

“The effect of ASIs on RCC needs to be studied further. For now, results suggest that for patients with metastatic RCC who are hypertensive at baseline, ASIs may be the best choice of antihypertensive therapy,” McKay said.

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