Ther Clin Risk Manag. 2009 Oct;5(5):699-706. Epub 2009 Sep 15.
Role of everolimus in the treatment of renal cell carcinoma.
George S, Bukowski RM.
University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA.
therapeutic options in metastatic renal cell carcinoma have been
recently expanded by the discovery of the VHL gene, the mutation of
which is associated with development of clear cell carcinoma, and
overexpression of the angiogenesis pathway, resulting in a very
vascular tumor. This breakthrough in science led to the development of
a variety of small molecules inhibiting the VEGF-dependent angiogenic
pathway, such as sunitinib and sorafenib. These agents prolong overall
and progression-free survival, respectively. The result was the
development of robust front-line therapies which ultimately fail and
are associated with disease progression. In this setting, there existed
an unmet need for developing second-line therapies for patients with
refractory metastatic renal cell carcinoma (MRCC). Everolimus (RAD 001)
is an oral inhibitor of the mammalian target of rapamycin (mTOR)
pathway. The double-blind, randomized, placebo-controlled phase III
trial of everolimus (RECORD-1) conducted in MRCC patients after
progression on sunitinib or sorafenib, or both, demonstrated a
progression-free survival benefit favoring the study drug (4.9 months
vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P </= 0 0.001).
Everolimus thus established itself as a standard of care in the
second-line setting for patients with MRCC who have failed treatment
with VEGF receptor inhibitors.