What is the role of axitinib (Inlyta) in the treatment of renal cell carcinoma (RCC)?

Updated: Jun 08, 2020
  • Author: Kush Sachdeva, MD; Chief Editor: E Jason Abel, MD  more...
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Axitinib (Inlyta) inhibits tyrosine kinase receptors including VEGFR-1, VEGFR-2, and VEGFR-3. Axitinib is 50-450 times more potent than first-generation VEGF inhibitors in inhibiting those VEGF receptors. The FDA approved axitinib in January 2012 for treatment of advanced RCC after failure of one prior systemic therapy.

The approval was based on a single efficacy study, (AXIS trial), in which axitinib extended progression-free survival by 2 months more than sorafenib (6.7 mo vs 4.7 mo, P < 0.0001) and produced a superior objective response rate (19.4% vs 9.4%). [60] AXIS was a randomized, controlled, open-label, multicenter phase 3 trial in 723 patients with advanced renal cell carcinoma who had failed one previous therapy. Severe toxicity requiring discontinuation of therapy was less prevalent in the axitinib group (4% vs 8%). This study is the only published phase 3 head-to-head comparison of VEGF-targeted agents.

Previous studies of combination therapy with first-generation VEGF inhibitors and PD-1 checkpoint inhibitors have reported excessive toxicity. However, in an ongoing phase Ib trial by Atkins et al, treatment with the combination of axitinib plus pembrolizumab proved tolerable and yielded an objective response in 38 of 52 (73%) patients with treatment-naive metastatic RCC. Median progression-free survival (PFS) was 20.9 months, and median duration of response in responders was 18.6 months. No unexpected toxicities were observed. [61, 62]

In the study, axitinib 5 mg was administered orally twice daily, with pembrolizumab 2 mg/kg given intravenously every 3 weeks. A phase 3 trial that is currently in progress is comparing the combination of axitinib and pembrolizumab (200 mg IV every 3 weeks) with sunitinib monotherapy. [62]

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