Precision Oncology: Identifying Predictive Biomarkers for the Treatment of Metastatic Renal Cell Carcinoma

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Abstract

The recent FDA approval of multiple new pharmaceutical agents for metastatic renal cell carcinoma (RCC) has left physicians with several options for first- and second- line therapy. With limited head-to-head comparisons, however, there is a paucity of evidence to recommend the use of one agent over another. To address this knowledge gap, Voss et al. identified serum biomarkers from specimens collected during the RECORD-3 trial, a comparative study of first-line sunitinib versus first-line everolimus. Of the biomarkers identified, the 5 most strongly associated with first-line everolimus progression-free survival (PFS1L) were combined to form a composite biomarker score (CBS). The CBS was significantly associated with everolimus PFS1L in multivariate regression analysis. This study is an example of the additional value offered by a randomized trial with prospective biospecimen collection and a significant step towards identifying predictive biomarkers for the treatment of metastatic RCC. As further comparative trials are performed, it will be essential that biomarkers are appropriately identified and validated in order to further the goal of precision oncology.

Keywords: Carcinoma, Renal Cell, Biomarker
Therapeutic options for patients with metastatic renal cell carcinoma (RCC) are expanding rapidly. Currently, eleven FDA-approved agents are available for the treatment of RCC. The majority of these disrupt metabolic or proliferative pathways such as vascular endothelial growth factor (VEGF; bevacizumab), its receptor (VEGFR; axitinib, pazopanib, sorafenib, sunitinib, cabozantinib, lenvatinib), or the mammalian target of rapamycin (mTOR; everolimus, temsirolimus) while two others (nivolumab and interleukin-2) bolster the patient’s anti-tumor immune response (Table 1) (1–13). Unfortunately, the overall survival (OS) and progression free survival (PFS) benefits of these agents in the first-line setting have largely been demonstrated with respect to either placebo or interferon-alpha monotherapy as the comparator arm in phase III randomized controlled trials (RCTs)(3–6, 8, 9, 13) (Table 1). To date, only two phase III RCTs have directly compared tyrosine kinase inhibitors (TKI) in treatment-naïve metastatic RCC and both trials failed to identify a single best choice for first-line therapy(14, 15).

Table 1
Table 1
FDA approved therapies for RCC with their pivotal trial parameters.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986829/

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