In 2011, an estimated 61,000 patients in the United States were diagnosed with cancer of the kidney, with approximately 60% of the cases diagnosed in men.1 The disease caused slightly more than 13,000 deaths. The incidence of renal cell carcinoma (RCC) is increasing, more than doubling between 1950 and 2001, some of which can be explained by better detection with modern imaging techniques, but other reasons are not fully understood.2,3 Approximately 85% of RCC are of the clear cell type.2

The Treatment Landscape of RCC, Past and Present
Small renal tumors are amenable to surgical resection by partial or radical nephrectomy, or in some cases, less invasive techniques, with long-term survival achieved in 80%–95% of patients.2 Even locally invasive disease can be successfully managed in about 65% of cases. Historically, cytotoxic chemotherapy for advanced (stage IV) RCC produced responses in fewer than 10% of patients.4 Standard therapy for advanced RCC involves cytoreductive nephrectomy, if possible. Unlike other metastatic malignancies, resection of the primary RCC tumor is associated with improved survival.2 This observation led to investigations of immune mechanisms of tumorigenesis and treatment in the 1990s. It is now understood that RCC impairs T-cell mediated tumor immunity.5 High-dose aldesleukin (interleukin-2, IL-2) produced complete responses (some lasting one to three years) and an overall response rate of 28%, but toxicity is high. It still is a valid option in certain populations with low-volume disease and good performance status.5,6

A retrospective review of various trials with interferon-alfa (INF-α) found the median overall survival (OS) to be about 13 months.7 Based on these observations, INF-α was used as the control group for many of the Phase 3 clinical trials of targeted agents that began about ten years ago.

Continue Reading

Since that time, seven targeted therapies have been approved by the FDA for advanced RCC:

     1. Axitinib (inhibitor of VEGFR-1, -2 and -3), 2012
     2. Bevacizumab (inhibitor of VEGF) with IFN-α, 2009
     3. Everolimus (inhibitor of mTOR), 2009
     4. Panzopanib (RTKI for VEGFR and PDGFR), 2009
     5. Sorafenib (RTKI for VEGF), PDGF and BRAF), 2005
     6. Sunitinib (RTKI for PDGF and VEGF), 2006
     7. Temsirolimus (mTOR inhibitor), 2007
[mTOR=inhibitor of mammalian target of rapamycin; PDGF=platelet-derived growth factor; RTKI=receptor tyrosine kinase inhibitor; VEGFR=vascular endothelial growth factor; VEGFR=VEGF receptor]