The Medical Management Of Metastatic Renal Cell Carcinoma: Integrating New Guidelines And Recommendations

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 30 Apr 2009 - 3:00 PDT

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UroToday.com - With five targeted agents approved for the treatment of mRCC (sorafenib, sunitinib, temsirolimus, everolimus, and bevacizumab plus IFN), medical management decisions for this disease have become complex. Several national and international panels of experts have published guidelines and recommendations to assist clinicians in selecting the best treatment for their patients. We reviewed four such publications from the European Association of Urology (EAU), the United States National Comprehensive Cancer Network (NCCN), the European Organisation for Research and Treatment of Cancer (EORTC) and the International Society of Geriatric Oncology (SIOG). During this review, three key questions emerged

1. Can treatment decisions be based on Phase III data alone?

Data from Phase III clinical trials are central to all guidelines but leave many questions unanswered. Patients with mRCC represent a heterogeneous population and many patient types are excluded from pivotal Phase III studies. Therefore, in addition to Phase III data, guidelines base their recommendations on additional forms of clinical evidence, such as expanded access studies, retrospective analyses, case studies and clinical experience.

2. Should treatment be tailored to individual patients?

Since no one agent will benefit all patient types, optimal selection of treatment for RCC should be based on a patient-focused approach that considers multiple patient, disease and treatment-related factors. The guidelines recognise the importance of such an individualised approach to therapy. For example, the NCCN guidelines specify that sorafenib should be considered as a first-line option for selected patients.

One important patient population often under-represented in clinical trials is the elderly. The median age at RCC diagnosis is 65 years yet less than 40% of patients included in Phase III studies of targeted agents were over 65 years old. Elderly patients have complex physiology and underlying comorbidities, which may impact their clinical response and tolerance to therapy. The multi-tyrosine kinase inhibitor (TKI), sorafenib, has similar efficacy in both elderly and younger patient populations. Similarly, the rates of adverse events associated with sorafenib therapy in older patients were comparable with those in their younger counterparts.

3. Can clinical benefit be extended by sequential use of targeted agents?

Sequencing of targeted therapies may prove to be the most cost effective and least toxic way to get the most from the five targeted agents available to us. The guidelines recognise the importance of sequencing targeted therapy and a growing body of retrospective and prospective evidence indicates that sequential use of TKI's is a viable option. The EORTC group also cite accumulating retrospective data that suggests patients treated with sorafenib followed by sunitinib have longer overall disease control than patients treated with the reverse sequence.

To summarise, targeted therapies have had a dramatic impact on the medical management of patients with mRCC. The published guidelines for their use are based on Phase III clinical data alongside additional forms of evidence and highlight that therapy should be tailored to each patient based on individual clinical profiles in order to maximise clinical benefit.

Written by Joaquim Bellmunt and Marta Guix as part of Beyond the Abstract on UroToday.com

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