Angiotensin system inhibitors prolong survival of patients with metastatic renal cell carcinoma, according to a retrospective study being presented at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.
Patients taking one of these antihypertensive agents lived on average about 10 months longer than their counterparts not taking them, reported lead author Dr. Rana R. McKay, a clinical oncology fellow at the Dana-Farber Cancer Institute in Boston.
Dr. Rana McKay
In analyses stratified according to type of cancer treatment, benefit was restricted to patients whose cancer was being treated with agents that target vascular endothelial growth factor (VEGF), which is known to have interactions with the angiotensin system that affect cell proliferation and angiogenesis.
"This is the largest analysis to our knowledge evaluating the role of ASIs [angiotensin system inhibitors] on outcomes not just in metastatic renal cell carcinoma but for all cancers," Dr. McKay commented in a press briefing held before the symposium.
"We demonstrated that ASI users had significantly improved survival when compared to ASI nonusers, even after adjustment for the development of treatment-associated hypertension. ASIs appear to have a synergistic activity in patients on VEGF-targeted therapy," she said.
"Although lab-based and prospective studies are required to explore this relationship further, in patients with metastatic renal cell carcinoma who warrant an antihypertensive agent, ASIs may be the agent of choice for patients without any contraindications for their use," Dr. McKay proposed.
It is noteworthy that nearly half of the patients studied had hypertension at baseline, according to press briefing moderator Dr. Charles J. Ryan, a professor at the University of California, San Francisco, and leader of the genitourinary medical oncology program.
"There is quite a significant effect here, and it really makes sense given the mechanism of action of VEGF-targeted therapy. I’m sure there will be a lot of interest going forward with this in prospective data," he commented.
There is good rationale for investigating ASIs – a collective term for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) – in renal cell carcinoma, according to Dr. McKay.
"VEGF is an established target in metastatic kidney cancer. Increasing evidence suggests that angiotensin II is an important regulator of vascular homeostasis and modulates VEGF-dependent angiogenesis," she explained.
The investigators reviewed data from a clinical trials database of 4,736 patients with metastatic renal cell carcinoma treated on Pfizer-sponsored phase II and III clinical trials between 2003 and 2013.
The largest share of patients (42%) had intermediate-risk disease according to IMDC (International mRCC Database Consortium) risk classification. In all, 70% had undergone nephrectomy, and 48% had hypertension at baseline.
Overall, 31% of patients in the cohort were using ASIs at baseline or started one in the first 30 days of their trial. Another 17% were using some other type of antihypertensive, and the remaining 52% were not using any.
In the entire study cohort, overall survival was 27 months for ASI users and 17 months for all other patients (hazard ratio, 1.21; P = .0009).
Among patients whose cancer was being treated with VEGF-targeted therapy, overall survival was better for ASI users than for all other patients (HR, 1.36; P less than .0001). But there was no such benefit for patients whose cancers were being treated with mammalian target of rapamycin (mTOR) inhibitors or for patients whose cancer was being treated with interferon-alpha.
In additional findings, among patients taking any kind of antihypertensive and receiving VEGF-targeted therapy, survival was better for ASI users than for users of other types of antihypertensives (31 vs. 22 months; HR, 1.38; P = .0003).
Dr. McKay disclosed no relevant conflicts of interest.