Axitinib in metastatic renal cell carcinoma

Abstract

Axitinib is the most recent targeted therapy approved by the US FDA and EMA in the treatment of metastatic renal cell carcinoma (mRCC). It is a second-generation, orally available, potent tyrosine kinase inhibitor targeting selectively VEGF receptor (VEGFR)-1, -2 and -3, resulting in inhibition of angiogenesis, metastasis and tumor growth. Based on the results of a randomized pivotal Phase III clinical trial, axitinib stands as one of the two recommended agents for patients with mRCC who progressed after first-line tyrosine kinase inhibitor therapy. Its potent and selective inhibition of VEGFR was the rationale for its development in the second-line setting after failure of prior cytokines or sunitinib. Here we examine the preclinical and clinical data of axitinib for mRCC, and its use in the treatment algorithm.

Keywords:

• axitinib
• clear cell
• metastatic renal cell carcinoma
• VEGFR TKI

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Targeting the VEGF receptor (VEGFR) pathway is a key therapeutic option in the treatment of metastatic renal cell carcinoma, as it shows a proven benefit in terms of overall survival in the first-line setting.

• Axitinib is a second-generation tyrosine kinase inhibitor exhibiting a more potent inhibition of VEGFR-1, -2 and -3 than the first-generation tyrosine kinase inhibitor.

• Axitinib has been approved as a single agent in the second-line metastatic renal cell carcinoma patients following a first-line therapy with sunitinib or cytokines.

• Axitinib was approved as it showed significant improvement of progression-free survival, compared to sorafenib.

• This provides evidence favoring lack of cross-resistance between different VEGFR inhibitors.