Frontline Treatment Approaches in Advanced RCC

Deciding on a frontline treatment approach for patients with renal cell carcinoma (RCC) depends on many factors. This decision can be aided by available treatment algorithms, which help determine the patient's prognosis and assess various clinical features, such as anemia, performance status, calcium levels, lactate dehydrogenase (LDH), leukocytosis, and thrombocytosis.

A previously untreated individual with poor performance status, poor prognosis, and relatively short survival should generally not undergo cytoreductive nephrectomy, states Eric Jonasch, MD. The net absolute gain of survival from a cytoreductive nephrectomy is approximately 1.5 to 2 months, says Jonasch.

Systemic therapy may help reduce the impact of disease burden on the patient’s overall performance status, says Jonasch. Major systemic therapies for RCC include mTOR inhibitors, TKIs, and high-dose interleukin-2 (IL-2), which have the potential to produce durable responses but is not without toxicity. IL-2 may not be feasible in a patient with poor performance status, notes Jonasch.

When deciding between TKIs and mTOR inhibition, a number of factors should be considered. Randomized phase III data have demonstrated the superiority of temsirolimus, an mTOR inhibitor, over interferon in individuals with poor-risk disease. TKIs, such as sunitinib or pazopanib, may also be used in this setting; however, level 1 evidence comparing a TKI to temsirolimus is currently not available.

In the frontline setting for those at low- or intermediate-risk, sunitinib and pazopanib are effective options for most patients with advanced RCC, comments Jonasch. Unique factors can be used to help select which agent may be more appropriate. Patients with advanced symptoms who require rapid tumor shrinkage may benefit more from sunitinib, explains Jonasch. Additionally, pazopanib may not be appropriate in patients with liver enzyme abnormalities.