Immature blood vessels linked to poor sunitinib response

By Afsaneh Gray, medwireNews Reporter

Patients with clear-cell renal cell carcinoma (RCC) with relatively mature blood vessels respond better to sunitinib and have fewer metastatic sites than those with immature vessels, a study has found.

Not all patients with metastatic (m)RCC benefit from sunitinib, or from other tyrosine kinase inhibitors, and “[t]here is thus a great impetus to discover biomarkers in RCC that can identify the subpopulation of patients who would gain the maximal benefits from a given drug”, say lead author Chun Il Kim (Keimyung University School of Medicine, Daegu, Korea) and colleagues.

They add that the role of pericytes – cells that wrap around the endothelial cells of capillaries and venules – in sunitinib response has, until now, not been adequately explored.

The researchers took tissue samples from 29 patients with mRCC who were being treated with sunitinib after radical nephrectomy or biopsy. CD31 was used to identify endothelial cells in the samples and anti-α smooth muscle actin (αSMA) to identify pericytes.

The majority of patients had intermediate or poor prognoses, and 21 of them had metastasis at the time of diagnosis. Median treatment duration was 8.0 months, and patients were followed up for a median of 29.1 months.

By the end of the study, 51.7% of patients were classified as having partially responded to therapy, 10.4% had stable disease and 37.9% had disease progression.

Nine cases were identified as having low pericyte coverage of less than 40%. In the group with high pericyte coverage, the number of metastatic sites was comparatively smaller. In addition, this group fared better in terms of sunitinib response rates.

However, although numerically higher in the high- than low-pericyte coverage group, median overall survival (16.8 vs 7.0 months) and median progression-free survival (8.2 vs 2.0 months) did not differ significantly between the two groups.

Kim and colleagues suggest that there could be several reasons why progression-free survival and overall survival were not found to be related to pericyte coverage in their study. Firstly, tumours often develop resistance to anti-angiogenic drugs such as sunitinib, and 20.6% of patients went on to receive second-line therapies that could have confounded their analysis. Also the sample number of their study may have been too small to detect such a difference.

Nonetheless, writing in Urologia Internationalis, the authors conclude: “The results of this study suggest that immature microvessels which are not covered by pericytes may be a useful prognostic factor for evaluating sunitinib treatment in patients with mRCC.”

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