FROM THE LITERATURE
RENAL CELL CARCINOMA:
mTOR Inhibition Produces Impressive Results After Disease Progression
on VEGF TKIs

RAD001 (with the proposed brand name of Afinitor) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma (mRCC). Results of a phase III, double-blind, randomized, placebo-controlled trial of everolimus in 410 patients with mRCC whose disease had progressed on treatment with VEGF receptor tyrosine kinase inhibitors (sunitinib, sorafenib, or both) have demonstrated that treatment with everolimus prolongs PFS (the primary endpoint) relative to placebo in this patient population. The study drug and the placebo were given in conjunction with best supportive care. Findings: Results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was halted early after 191 progression events were observed, 37% events in everolimus group and 65% in the placebo group (HR 0.30, p<0.0001); median PFS 4.0 months vs. 1.9 months favoring everolimus. At the time of the analysis, median OS had not been reached for the everolimus group. As anticipated, A/Es were more frequently reported for everolimus but these were mostly grade 1 or 2.

Treatment with VEGF receptor tyrosine kinase inhibitors has provided a significant benefit to patients with mRCC but the therapy is not curative and a therapeutic option was lacking after progression on these agents. On the basis of the results of this trial, the authors feel that everolimus should now be considered as the standard-of-care for this population of mRCC patients.

Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372:449-456.

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