The clinical potential of temsirolimus in second or later lines of treatment for metastatic renal cell carcinoma

Abstract

An impressive variety of targeted therapies has been approved for the treatment of metastatic renal cell carcinoma (mRCC). Despite promising progress, there are still unmet clinical needs. The optimal sequence of these agents in the therapeutic setting has not yet been determined. Most available data address first- and second-line therapy of clear cell RCC. The mTOR inhibitor temsirolimus has been approved for first-line treatment of mRCC, and there are new data addressing the use of temsirolimus in later therapeutic lines. Temsirolimus has discerning features compared with other currently registered drugs, such as its intravenous administration route–providing predictable bioavailability and adherence to treatment–and potential benefit in nonclear cell histologies. Here, we review the available literature on temsirolimus, with reference to data also available for everolimus, to determine its clinical potential in mRCC.

Keywords::

• everolimus
• metastatic renal cell carcinoma
• mTOR inhibition
• nonclear cell RCC
• temsirolimus
• tyrosine kinase inhibitors
• VEGFR inhibitors

Financial & competing interests disclosure

F Stenner-Liewen has served as an advisor for Roche, Novartis, Pfizer, Bayer and GSK in the past. V Grünwald , has received honoraria from Roche, Novartis, GSK and Pfizer, and also has an advisory role with Roche, Novartis, Pfizer, GSK, Bayer and Astellas. R Greil has received scientific research support from Roche, Ratiopharm, Amgen and Novartis, and honoraria from Roche, Amgen, Novartis and BMS. He has served as an advisor for Roche, Merck, Amgen, Novartis, Takeda and Boehringer Ingelheim. C Porta has served as an advisor and/or speaker for Pfizer, GSK, Roche, Bayer, Aveo, Astellas, Novartis and Boehringer Ingelheim. He has also received research grants from Bayer and Novartis as well as clinical trial support from Pfizer.  Medical writing support was provided by Jean Scott, a freelance medical writer, and Rachel Mason at ACUMED (Tytherington, UK) and was funded by Pfizer Inc.

Key issues

• • VEGF-targeted therapy and mTOR inhibition are the main therapeutic principles of targeting mRCC today. In terms of mTOR inhibition, temsirolimus has found its place in the first-line setting for patients with poor prognosis, and everolimus has been approved for second line and later use for all prognostic subgroups.

• • To date, combining mTOR inhibition with VEGF-targeted therapy has failed in clinical trials due to increased toxicity without synergistic efficacy.

• • The selection of an individual therapy has become increasingly complex and it may be impossible to conduct all the trials needed to define the optimal sequence for each patient profile.

• • Despite a wealth of guidelines recommending standard therapies for first-, second- and even third-line treatment (e.g., ESMO guidelines), therapeutic decisions at each point of treatment will continue to be based on individual patient and tumor features.

Notes