Optimizing treatment of metastatic renal cell carcinoma by changing mechanism of action

Abstract

Novel targeted agents, such as VEGF receptor-tyrosine kinase inhibitors (VEGFR-TKIs) and mTOR inhibitors, have improved therapy for metastatic renal cell carcinoma. Sequential administration of agents with similar mechanisms of action has shown some efficacy in small retrospective studies; however, prospective Phase II studies have reached differing conclusions, and there is a current lack of prospective randomized data to validate this approach. Sequential administration of agents with different mechanisms of action has shown clinical efficacy in prospective trials, including a randomized Phase III study (RECORD-1) of the mTOR inhibitor everolimus, the only targeted agent recommended for use after VEGFR-TKI failure in metastatic renal cell carcinoma. Ongoing research will further define the relative merits of other sequences in terms of clinical outcome.

Keywords::

• everolimus
• mTOR inhibitor
• renal cell carcinoma
• sequence
• sorafenib
• sunitinib
• VEGFR-TKI

Financial & competing interests disclosure

James Larkin has served as a consultant or advisor for AVEO, Pfizer, Bayer Pharmaceuticals, GlaxoSmithKline and Novartis, and has received research funding from Pfizer, Bayer Pharmaceuticals and Novartis. Lisa Pickering has served as a consultant or advisor for Pfizer, Novartis and GlaxoSmithKline, has received research funding from Pfizer, Novartis and Bayer Pharmaceuticals, and has received other remuneration from Pfizer and Bayer Pharmaceuticals. Charles Swanton has acted as an advisor for and received research funding from Novartis. The authors have no other 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 apart from those disclosed.

Medical writing support was provided by Scientific Connexions (PA, USA) and ApotheCom (PA, USA), and funded by Novartis Pharma (Basel, Switzerland).