Abstract
ABSTRACT Therapies currently available for treatment of patients with metastatic renal cell carcinoma (mRCC) include those that target the VEGF pathway and the mTOR pathway. VEGF pathway inhibitors include the multi-targeted receptor tyrosine kinase inhibitors sunitinib, sorafenib, pazopanib, and axitinib (VEGFr-TKIs) and the monoclonal antibody bevacizumab. The mTOR inhibitors include everolimus and temsirolimus. The international clinical guidelines recommend sunitinib, pazopanib, and bevacizumab (plus interferon-a) as first-line therapies for patients with mRCC who have a good prognosis and temsirolimus for patients who have a poor prognosis. Recently reported results of the COMPARZ and PISCES studies demonstrated that patients favor pazopanib over sunitinib as first-line treatment for mRCC based on better general quality of life. Everolimus is recommended for treatment of patients who failed previous VEGFr-TKI therapy. Sorafenib, sunitinib, and pazopanib are recommended for cytokine-refractory patients and axitinib is recommended for treatment of patients who failed previous cytokine or VEGFr-TKI therapy. Approved treatments are not curative; median overall survival remains suboptimal and most patients with mRCC who are treated with VEGF-targeted agents or mTOR inhibitors will eventually develop resistance and subsequently experience disease progression. With the primary goal of optimizing the treatment of patients with mRCC, multiple agents targeting various pathways are currently in development. These include targeted immunotherapeutics as well as innovative drugs directed to novel targets that might be biologically relevant for this disease, like cMET, Tie2, ALK1/ENG, PI3K, Akt, mTORC1/2 inh. Looking to the future, it will be imperative, as well, to identify predictive biomarkers to further refine treatment options and to identify the optimal treatment for individual patients with mRCC. Disclosure: E. Calvo: Research funding from Novartis, Pfizer, GSK, Roche.
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