For good or intermediate risk patients (see discussion fromhttp://talkabouthealth.com/for-kidney-cancer-patients-what-can-be-learned-from-blood-tests-and-what-in-particular-are-you-watching-for
) with metastatic clear cell RCC, results of randomized phase III clinical trials support a choice for first line anti-angiogenic (vascular endothelial growth factor (VEGF) pathway targeted therapy) between the oral tyrosine kinase inhibitors (TKI’s) sunitinib or votrient versus the combination of bevacizumab, given by iv infusion every two weeks, paired with IFN administered as a subcutaneous injection three times weekly. Outcomes of separately conducted studies with sunitinib, pazopanib and the bevacizumab/IFN combination are not sufficiently different to suggest a preferred agent. For my own patients, I see a definite preference for the oral agents that generally require less frequent clinic visit and allow a more flexible schedule than for bevacizumab/IFN. Many patients travel significant distances to be evaluated and treated at our center, or prioritize travel and vacation plans with the knowledge they have an incurable cancer and appreciate the convenience of the oral agents.
Results from head to head trials of pazopanib versus sunitinib (the PISCES and COMPARZ trials) have been reported in 2012. Key findings demonstrated statistically equivalent anti-tumor efficacy for the two TKI’s with a side effect profile favoring pazopanib. These emerging comparative results may sway providers to recommend pazopanib as a preferred agent over sunitinib for primary therapy of clear cell RCC.
For poor risk RCC patients, temsirolimus is the preferred agent based on a phase III study (the ARCC trial) demonstrating a survival benefit for temsirolimus versus IFN in this patient population.
There is less clinical data to guide therapy choices for non-clear cell RCC tumors. Subgroup analysis of the ARCC study of temsirolimus versus IFN demonstrated a survival benefit in non-clear cell histologies. Although the study only enrolled poor risk patients, I generally view mTOR inhibitors as the drug class of choice for first line treatment of non-clear cell RCC, recognizing good performance patients will inevitably receive TKI’s in the second line. Retrospective and subgroup analyses suggest TKI’s have less potency for non-clear cell RCC tumors than for the clear cell histology. An ongoing comparative study of the oral mTOR inhibitor everolimus versus sunitinib as first line treatment for non-clear cell RCC will help to define the best available agent for these patients.