Angiotensin system inhibitor use improves metastatic RCC survival outcomes

By Shreeya Nanda, Senior medwireNews Reporter

Use of angiotensin system inhibitors (ASIs) is associated with significant survival benefits in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era, research findings indicate.

In this pooled analysis of phase II and phase III clinical trial data, median overall survival (OS) was 26.68 months in the 1487 patients who received ASI therapy, either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, at baseline or within 30 days of initiation of the study treatment.

This was significantly longer than the median OS of 18.07 months in the 783 patients using non-ASI antihypertensive medication, such as β-blockers and diuretics, with an adjusted hazard ratio (HR) of 0.838. And also longer than the 16.72 months observed in the 2466 participants not treated with any antihypertensive agents, with an adjusted HR of 0.810.

Median progression-free survival (PFS) was also significantly improved in ASI users compared with those treated with other antihypertensive drugs, at 8.34 versus 6.70 months. But the difference was not significant when ASI users were compared with nonusers.

The survival benefit accorded by ASI use was restricted to individuals receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, but not mammalian target of rapamycin-targeted therapy or interferon-α, with a median OS of 31.12 versus 20.21 months in ASI users compared with nonusers.

ASI use also resulted in significantly prolonged survival in the subset of patients who developed VEGF treatment-associated hypertension, with a median OS of 33.19 versus 24.64 months in ASI users versus nonusers. And median PFS was significantly better in ASI users than in nonusers too, at 10.92 versus 9.05 months.

“We postulate that this is likely related to a synergistic interaction between ASIs and VEGF-targeted therapy given that these agents are thought, at least in part, to augment a similar pathway”, write Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues in Clinical Cancer Research.

They conclude: “Though our study was based on a pooled analysis of prospectively collected data, further studies are warranted to verify our observations and inform the clinical practice of ASI use in combination with VEGF targeted agents in patients with mRCC.”

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