Prognostic and predictive biomarkers for RCC emerge

Although prognostic biomarkers have been identified in renal cell cancer (RCC), none have been routinely applied in the clinic. Furthermore, no predictive biomarkers are used to identify patients who might benefit from a given treatment. New research from a team led by John Heymach and published in The Lancet Oncology has addressed this gap in RCC biomarker research.

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The team retrospectively investigated the concentrations of several circulating cytokines and angiogenic factors (CAFs) in the plasma of patients enrolled in two clinical studies (one phase II, one phase III). Both trials examined the effect of pazopanib (an angiogenesis inhibitor that targets several receptor tyrosine kinases) on the progression-free survival (PFS) of patients with metastatic RCC. As these patients were either receiving treatment or not, the identification of predictive biomarkers for pazopanib was also a possibility.

Seventeen CAFs identified in previous studies were screened using a subsample of patients in the phase II trial. Subsequently, seven CAFs were confirmed to have a correlation with PFS in all the phase II patients. In the final study stage, these CAFs—IL-6, IL-8, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), tissue inhibitor of metalloproteinases 1 (TIMP-1), E-selectin and osteopontin—were validated using the phase III data (n = 344).

The validation stage revealed that IL-8, HGF, osteopontin and TIMP-1 are associated with PFS in the pazopanib group. In the placebo group, IL-6, IL-8 and osteopontin were identified as prognostic biomarkers.

The most interesting result from the study is arguably the identification of IL-6 as a predictive biomarker for response to pazopanib. Unlike the treatment group (P = 0.445), patients in the placebo group with high concentrations of IL-6 had a shorter PFS than those with low IL-6 (P <0.0001). Furthermore, IL-6 seems more predictive of PFS in patients who had previously undergone cytokine-based therapy than those who did not, which might have clinical implications.

These encouraging results indicate we are nearing an era whereby accurate and informative biomarkers will be available to benefit patients with RCC.