Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 15/2009

01-10-2009 | ADis Drug Profile

Everolimus

In Advanced Renal Cell Carcinoma

Authors: Karly P. Garnock-Jones, Gillian M. Keating

Published in: Drugs | Issue 15/2009

Login to get access

Abstract

  • ▲ Everolimus is an orally administered, targeted therapy indicated for the treatment of advanced renal cell carcinoma. It inhibits the mammalian target of rapamycin, an integral component of multiple pathways involved in cell growth and proliferation.
  • ▲ Median progression-free survival was significantly longer with everolimus 10 mg once daily than with placebo in both second interim (4.0 vs 1.9 months) and updated (4.9 vs 1.9 months) analyses of a randomized, double-blind, placebo-controlled, multicentre, phase III trial in patients with metastatic renal cell carcinoma that had progressed while receiving sunitinib and/or sorafenib treatment.
  • ▲ At the second interim analysis, median overall survival was 8.8 months for placebo recipients; at this analysis, overall survival had not yet been reached for everolimus recipients.
  • ▲ With regard to objective response at the second interim analysis, 64% of everolimus and 32% of placebo recipients had either a partial response (1% and 0%) or stable disease (63% and 32%).
  • ▲ The tolerability profile of everolimus was largely manageable in the phase III trial, with most treatment-related adverse events being of grade 1 or 2 severity.
Literature
1.
Bellmunt J, Guix M. The medical management of metastatic renal cell carcinoma: integrating new guidelines and recommendations. BJU Int 2009 Mar; 103(5): 572–7PubMedCrossRef
2.
Kroog GS, Motzer RJ. Systemic therapy for metastatic renal cell carcinoma. Urol Clin North Am 2008 Nov; 35(4): 687–701PubMedCrossRef
3.
4.
Escudier B. Signaling inhibitors in metastatic renal cell carcinoma. Cancer J 2008 Sep/Oct; 14(5): 325–9PubMedCrossRef
5.
Escudier B, Thompson JA. Mechanism of action of everolimus in renal cell carcinoma. Med Oncol 2009; 26 Suppl. 1: S32–9CrossRef
6.
7.
Dunn C, Croom KF. Everolimus: a review of its use in renal and cardiac transplantation. Drugs 2006; 66(4): 547–70PubMedCrossRef
8.
9.
Abraham RT, Gibbons JJ. The mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy. Clin Cancer Res 2007 Jun 1; 13(11): 3109–14PubMedCrossRef
10.
Boulay A, Zumstein-Mecker S, Stephan C, et al. Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 2004 Jan 1; 64(1): 252–61PubMedCrossRef
11.
Schuler W, Sedrani R, Cottens S, et al. SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo. Transplantation 1997 Jul 15; 64(1): 36–42PubMedCrossRef
12.
Fingar DC, Salama S, Tsou C, et al. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev 2002 Jun 15; 16(12): 1472–87PubMedCrossRef
13.
Fingar DC, Richardson CJ, Tee AR, et al. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol 2004 Jan; 24(1): 200–16PubMedCrossRef
14.
Shinohara ET, Cao C, Niermann K, et al. Enhanced radiation damage of tumor vasculature by mTOR inhibitors. Oncogene 2005 Aug 18; 24(35): 5414–22PubMedCrossRef
15.
Lane HA, Wood JM, McSheehy PM, et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res 2009 Mar 1; 15(5): 1612–22PubMedCrossRef
16.
17.
O’Donnell A, Faivre S, Burris HA, et al. Phase I pharmaco-kinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol 2008 Apr 1; 26(10): 1588–95PubMedCrossRef
18.
Tabernero J, Rojo F, Calvo E, et al. Dose- and schedule-dependent inhibition of the mammalian target of rapamyci pathway with everolimus: a phase I tumour pharmacodynamic study in patients with advanced solid tumours. J Clin Oncol 2008; 26(10): 1603–10PubMedCrossRef
19.
Tanaka C, O’Reilly T, Kovarik JM, et al. Identifying optimal biologic doses of everolimus (RAD001) in patients with cancer based on the modeling of preclinical and clinical pharmacokinetic and pharmacodynamic data. J Clin Oncol 2008 Apr 1; 26(10): 1596–602PubMed
20.
21.
O’Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006 Feb 1; 66(3): 1500–8PubMedCrossRef
22.
Rosenberg JE, Weinberg VK, Claros C, et al. Phase I study of sorafenib and RAD001 for metastatic clear cell renal cell carcinoma [abstract no. 5109]. J Clin Oncol 2008 May; 26 (15 Suppl., Part I of II): 276S
23.
Kovarik JM, Hartmann S, Figueiredo J, et al. Effect of food on everolimus absorption: quantification in healthy subjects and a confirmatory screening in patients with renal transplants. Pharmacotherapy 2002 Feb; 22(2): 154–9PubMedCrossRef
24.
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 Aug 9; 372(9637): 449–56PubMedCrossRef
25.
26.
Amato RJ, Jac J, Giessinger S, et al. A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer 2009 Jun 1; 115(11): 2438–46PubMedCrossRef
27.
Jac J, Amato RJ, Giessinger S, et al. A phase II study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic renal cell carcinoma which has progressed on tyrosine kinase inhibition therapy [abstract no. 5113]. J Clin Oncol 2008; 26 (15 Suppl. Pt 1): s277. Plus poster presented at the 44th Annual Meeting of the American Society of Clinical Oncology; 2008 May 30–Jun 3; Chicago (IL)
28.
Whorf RC, Hainsworth JD, Spigel DR, et al. Phase II study of bevacizumab and everolimus (RAD001) in the treatment of advanced renal cell carcinoma [abstract no. 5010]. J Clin Oncol 2008 May; 26 (15 Suppl., part I of II): 252s
29.
30.
Metadata
Title
Everolimus
In Advanced Renal Cell Carcinoma
Authors
Karly P. Garnock-Jones
Gillian M. Keating
Publication date
01-10-2009
Publisher
Springer International Publishing
Published in
Drugs / Issue 15/2009
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/11203770-000000000-00000

Other articles of this Issue 15/2009

Drugs 15/2009 Go to the issue

Adis Drug Evaluation

Lapatinib

Adis Drug Evaluation

Lidocaine 5% Medicated Plaster

Adis Drug Profile

Saxagliptin

Current Opinion

Do Inhaled Anticholinergics Increase or Decrease the Risk of Major Cardiovascular Events?

Leading Article

Newer Biological Agents in the Treatment of Rheumatoid Arthritis

Review Article

African American Kidney Transplantation Survival