San Francisco, CA—The use of angiotensin system inhibitors (ASIs) improved survival in patients with metastatic renal-cell carcinoma (mRCC) by 9 months, according to a retrospective pooled analysis of several clinical trials presented at the 2014 Genitourinary Cancers Symposium. Survival was further improved if patients were also taking vascular endothelial growth factor (VEGF) receptor–targeted agents.
“Based on results of this study, an ASI should be considered for patients with metastatic renal-cell carcinoma who need an antihypertensive therapy and do not have any contraindications that preclude their use, especially in patients receiving VEGF-targeted treatments,” stated lead investigator Rana R. McKay, MD, Clinical Oncology Fellow, Dana-Farber Cancer Institute, Boston. “However, it is too early to determine if ASIs should be used for patients with metastatic renal-cell carcinoma who do not have coexisting hypertension or another medical condition to warrant ASI treatment.”
VEGF is an established target in mRCC, Dr McKay said. ASIs include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which act on the renin-angiotensin system and are used to treat hypertension (as well as other conditions). Recent research suggests that the peptide hormone angiotensin II modulates VEGF-depending angiogenesis. These data are intriguing and need confirmation in a larger prospective study, stated the investigators.
The study—the largest retrospective analysis to date evaluating the role of ASIs on outcomes in patients with cancer—was based on a database of 4736 patients with mRCC participating in phase 2 and 3 clinical trials conducted between 2003 and 2013. ASI use was defined as taking an ASI within days 0 to 30 of cancer treatment initiation. Baseline hypertension was present in approximately 48% of all patients; 1487 patients were taking an ASI, and 783 were taking other antihypertensive agents.
Treatments for patients with mRCC included VEGF-targeted agents (such as sunitinib [Sutent], sorafenib [Nexavar], axitinib [Inlyta], bevacizumab [Avastin]), or an mTOR inhibitor (temsirolimus [Torisel]), and interferon.
Overall survival (OS) for patients receiving ASI treatment was 26.68 months versus 17 months for non-ASI users (hazard ratio [HR], 1.213; P <.009). In patients taking VEGF agents for mRCC, ASI use significantly prolonged OS: 31 months for ASI users versus 21.94 months for nonusers (HR, 1.38; P = .003).
Moreover, tumor shrinkage was more likely in patients receiving ASIs. The median progression-free survival was 8.3 months for ASI users versus 6.5 months for nonusers (P = .042).
Concomitant Use of VEGF and ASI Agents
A subgroup analysis of type of anticancer therapy showed that only concomitant VEGF and ASI use was associated with a significant survival benefit. This association was not seen with mTOR inhibitors or interferon, and it persisted in a multivariate analysis adjusted for a number of cofactors, including age, sex, type of mRCC therapy, the presence of bone metastases, and risk groups.
“The effect of ASIs on renal-cell carcinoma needs to be studied further. For now, results suggest that in patients with metastatic renal-cell
carcinoma who are hypertensive at baseline, ASIs may be the best choice of antihypertensive therapy,” Dr McKay said.