VEGF Versus mTOR in Non-Clear Cell RCC

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Approximately 15% to 20% of renal cell carcinomas (RCCs) can be categorized as non—clear cell histologies, including sarcomatoid, papillary, and chromophobe histologies. Results from studies such as the RECORD-3 and ESPN trials has been practice-changing for the treatment of patients with this type of histology, Sumanta Kumar Pal, MD, notes. Overall, these trials have found that VEGF TKIs are more effective than mTOR inhibitors in treating non–clear cell RCC.

In the ESPN trial, everolimus demonstrated an inferior overall survival (OS) compared with sunitinib in patients with non-clear cell metastatic RCC. Median progression-free survival (PFS) in the first-line with sunitinib was 6.1 versus 4.1 months with everolimus. The median OS with everolimus in the first-line setting was 10.5 months and was not reached for sunitinib.

In the RECORD-3 study, everolimus was not noninferior to sunitinib as a frontline therapy for metastatic RCC. The median PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR = 1.3). The median OS was 22.4 months for everolimus-sunitinib and 32.0 months for sunitinib-everolimus (HR = 1.2).

Dose and schedule adjustments can be made to minimize toxicity while maintaining efficacy with these treatments, Pal suggests. Overall, the most common toxicities associated with either an mTOR or VEGF inhibitor in the clinical trials were stomatitis, fatigue, diarrhea, and other cutaneous events. Saby George, MD, comments that he discontinues the medication if grade 4 toxicity occurs and considers dose reduction or discontinuation if an individual experiences multiple grade 2 toxicities or cumulative grade 2 toxicities.