The Role of Everolimus in Renal Cell Carcinoma.

Malek Meskawi,Pierre I Karakiewicz,Paolo Dell'Oglio,Roger Valdivieso,Vincent Trudeau,Alessandro Larcher

doi:10.15586/jkcvhl.2015.43

Abstract

Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

Highlights

Renal cell carcinoma (RCC) is the seventh leading cancer among men and the tenth among women in the United States
In 2015, an estimated 61,560 new cases of RCC were diagnosed in the United States [1].The pathogenesis of the dominant clear cell histological subtype of RCC is associated with a loss of the von Hippel-Lindau (VHL) gene function on chromosome 3p
Two subtypes of targeted therapies exist for the treatment of metastatic RCC (mRCC)

Summary

Introduction

Renal cell carcinoma (RCC) is the seventh leading cancer among men and the tenth among women in the United States. The use of first-, second-, and subsequent-line targeted therapies resulted in up to 2-year increase in the life expectancy of patients with mRCC [6]. Two subtypes of targeted therapies exist for the treatment of mRCC (tyrosine kinase inhibitor [TKI] and mammalian target of rapamycin inhibitors [mTORi]). Five TKIs (sunitinib, sorafenib, pazopanib, axitinib, and bevacizumab) and two mTORi (temsirolimus and everolimus) were approved for the treatment of mRCC [5, 7,8,9,10,11,12]. The disruption of mTOR pathway suppresses the progression of cancer cells through the inhibition of cell cycle and angiogenesis

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