The Role of Everolimus in Renal Cell Carcinoma
Malek Meskawi1, Roger Valdivieso1, Paolo Dell'Oglio1
1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
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.
Insights
Everolimus offers a survival benefit for metastatic clear cell renal cell carcinoma (RCC) patients after prior treatments. It remains a key option for third-line therapy, though newer drugs challenge its second-line use.
Area of Science:
- Oncology
- Pharmacology
Background:
- Everolimus (RAD001) is an oral inhibitor of mammalian target of rapamycin (mTOR) kinase.
- Metastatic renal cell carcinoma (RCC) treatment has evolved with targeted therapies.
- Sequential therapy strategies are crucial for managing advanced RCC.
Purpose of the Study:
- To evaluate the efficacy of everolimus in metastatic clear cell renal cell carcinoma (RCC).
- To establish everolimus's role in sequential treatment paradigms for RCC.
- To compare everolimus with placebo in a phase III trial for heavily pretreated RCC patients.
Main Methods:
- A phase III pivotal trial was conducted.
- Everolimus was administered to patients with metastatic clear cell RCC after failure of prior therapies.
- Survival outcomes were compared against a placebo group.
Main Results:
- Everolimus demonstrated a significant 3-month survival benefit compared to placebo.
- Current evidence supports everolimus as a third-line therapy option post-tyrosine kinase inhibitor (TKI) failure.
- In non-clear cell RCC, everolimus is recommended as second-line therapy after sunitinib.
Conclusions:
- Everolimus provides a survival advantage in specific RCC patient populations.
- Its role in third-line therapy for clear cell RCC is established.
- Emerging agents like nivolumab and cabozantinib present alternatives for second-line treatment.
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