Everolimus post-progression on tyrosine kinase inhibitors in metastatic renal cell carcinoma: A clinical review of patients demonstrating a durable response and the effective management of treatment toxicity

• Published in: Journal of clinical oncology Vol. 30; no. 5_suppl; p. 449
• Main Authors: Wilson, James M., Ramamurthy, Sindhu, Pedley, Ian D., McMenemin, Rhona
• Format: Journal Article
• Language: English
• Published: 10.02.2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.5_suppl.449

Abstract only 449 Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus has been licensed as a second line treatment in metastatic renal cell carcinoma (mRCC) following treatment failure with a tyrosine kinase inhibitor (TKI). A randomised placebo control trial of everolimus used in this setting demonstrated only a modest median progression free survival of 4.9 months (Motzer RJ, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116:4256-65). Methods: We present 2 patients with a prolonged treatment response - both encountered mTOR inhibitor specific adverse events, the management of which will be discussed. Results: Patient 1: A 47 year old man with mRCC, previously treated with the Atzpodien regimen followed by sunitinib. A radiological response was seen after 2 treatment cycles of Everolimus and has remained stable for 25 months to date. A triglyceride level of 32.2 mmol/l has responded to a 50% dose reduction, dietary advice and the addition of a fibrate without loss of disease control. Patient 2: A 62 year old man with mRCC initially treated with Interferon followed by sunitinib. He developed radiological evidence of pneumonitis after 2 months of everolimus but did not experience (G3) symptoms until 2 months later. Pneumonitis responded to treatment deferral and corticosteroids and did not recur when everolimus was reintroduced. He achieved 18 months of PFS. Conclusions: Everolimus can initiate prolonged periods of progression free survival when used after progression on a TKI. The treatment is well tolerated and adverse events can be easily managed to allow ongoing therapy. Our further investigation, including tumor gene profiling, of such patients will allow a more personalised approach in the management of mRCC and improved prognostication in the clinic.