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Angiotensin system inhibitors extended PFS, OS in renal cell carcinoma
Concomitant use of angiotensin system inhibitors was associated with longer PFS and OS among patients with metastatic renal cell carcinoma, according to results of a database analysis presented at the 2014 Genitourinary Cancers Symposium.
Rana McKay, MD, a clinical oncology fellow at Dana-Farber Cancer Institute, and colleagues aimed to evaluate the effect of angiotensin system inhibitors (ASIs) — including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) — on patient outcomes.
“There’s been increasing evidence to suggest that angiotensin II plays a role in various pathologic situations such as cell proliferation, inflammation, angiogenesis, tissue repair and carcinogenesis,” McKay said during a press conference. “These very commonly used agents, ACE inhibitors and ARBs, are known to augment the renin-angiotensin system pathway and decrease the action or production of angiotensin II, which has been implicated in some of these pathological processes. We know that VEGF plays a very important role in kidney cancer and the pathogenesis of kidney cancer. The impetus to do this analysis stemmed from some of that preclinical work.”
McKay and colleagues identified 4,736 patients through a database review of phase 2 and phase 3 trials occurring from 2003 to 2013.
Patients received sunitinib (Sutent, Pfizer; n=1,059); sorafenib (Nexavar, Bayer; n=772); axitinib (Inlyta, Pfizer; n=896); temsirolimus (Torisel, Wyeth; n=457); temsirolimus plus interferon alfa (n=208); bevacizumab (Avastin, Genentech) plus temsirolimus (n=393); bevacizumab plus interferon alfa (n=391); or interferon alfa alone (n=560).
Sixty-nine percent of patients were younger than 65 years, and 71% were male. Eighty-nine percent of patients had clear-cell histology and 70% had undergone a prior nephrectomy.
There were more intermediate-risk patients (42%) than favorable- (14%) or poor-risk (24%) patients, according to the International mRCC Database Consortium risk groups.
Twenty-nine percent of all patients also received an ASI at baseline or within the first 30 days of the study. The majority of them (84%) had baseline hypertension. Baseline hypertension was present in 33% of patients who did not receive an ASI.
Patients who received ASIs demonstrated longer median PFS (8.3 months vs. 6.5 months; HR=1.147; 95% CI, 1.044-1.259) and median OS (25.6 months vs. 17.3 months; HR=1.258; 95% CI, 1.123-1.409) than patients who did not receive ASIs.
After adjustments for age, sex, bone metastases and risk groups, the associations between ASIs and favorable PFS and OS were still significant.
“Though larger prospective studies are needed, based on the results of this study, an ASI should be considered for patients with metastatic renal cell carcinoma who need an antihypertensive and do not have any contraindications that preclude their use, especially in patients receiving VEGF-targeted treatments,” McKay said in a press release. “However, it is too early to determine if ASIs should be used for patients with metastatic renal cell carcinoma who do not also have hypertension or another medical condition to warrant ASI treatment.”
For more information:
McKay RR. Abstract #437. Presented at: 2014 Genitourinary Cancers Symposium; Jan. 30-Feb. 1, 2014; San Francisco.
Disclosure: The researchers report research funding and remuneration from, consultant roles with, employment or leadership positions with, and stock ownership in Aveo Pharmaceuticals, Exelixis, GlaxoSmithKline, Novartis, Panacea Pharmaceuticals and Pfizer.
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It’s quite interesting that 48% of the total population of patients analyzed in this study had baseline hypertension. There’s quite a significant effect here, which really makes sense given the mechanism of action of the ASIs and the mechanism of action of the VEGF-targeted therapies. I’m sure there will be a lot of interest in moving forward with testing this in a prospective manner.