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Report On Kidney Cancer Symposium - Algorithm For Systemic Therapies In Metastatic Disease

May 31, 2017

Is there still a role for cytokine therapy in the treatment of metastatic RCC? A qualified maybe was the response of the group to this question. Improvements in our ability to select patients that are more likely to respond to high dose IL-2 based on clinicopathologic parameters may permit continued selective utilization of cytokine therapy in the treatment of metastatic RCC. Patients with > 85% expression of carbonic anhydrase IX (CA9), clear cell histology, lack of granular elements, have been shown to have an increased likelihood of responding to cytokine therapy with high dose IL-2. Moreover, the activity of the targeted therapy agents (TKI's) has never been directly compared to high dose IL-2, therefore there is no evidence that they are "superior". In addition, there is no evidence to suggest that cytokines may have efficacy in the setting of TKI failures, and should be considered in addition to other experimental therapy. Pretreatment with TKI's may, in fact, augment the activity of subsequent immunotherapy.

A paradigm was proposed as an approach to the treatment of patients with metastatic RCC. For patients with non-clear cell histology, a clinical trial should be pursued, or therapy with sunitinib was recommended.

For patients with clear cell histology, they should be divided into good, intermediate, and poor prognostic categories based on MSKCC guidelines. Those with poor prognosis should be treated 1st line with temsirolimus (shown to be more effective than interferon in prolonging time to progression and survival in poor prognosis patients with metastatic RCC.) Good and intermediate prognosis patients should be stratified according to CA9 expression. High expressors (>85%) should be considered for cytokine therapy (or alternatively, TKI therapy). Low CA9 expressors should not be considered for cytokine therapy but instead should receive TKI therapy with sunitinib or sorafenib. Unlike cytokine therapy, CA9 expression by the tumor does not correlate with response to TKI therapy.

A word of caution was also raised that the currently commercially available CA9 antibody is not the same antibody that was used in the studies that correlated expression to response to IL-2. It will need validation before it can be recommended for use in the selection of patients for treatment with cytokine therapy.

Vertical (e.g. TKI plus bevacizumab) and horizontal (e.g. TKI plus mTOR inhibitor) trials are either ongoing or in development to assess what combinations improve outcomes in patients with metastatic RCC. There appears to be increased toxicity associated with this approach, thus dose reductions may be required. Furthermore, sequential therapy also holds promise. There has been evidence of some partial responses and stable disease to sunitinib in bevacizumab and sorafenib failures, and evidence of stable disease in response to sorafenib that was previously progressing on sunitinib.

Presented on May 5, 2007 at the Kidney Cancer Association's Second European International Kidney Cancer Symposium

Speakers:

-- M. Schmidinger, M.D., Vienna, Austria

-- B. Porta, M. D., Pavia, Italy

-- T. Eisen, M. D., Cambridge, England

Reported by UroToday Contributing Editor Christopher G. Wood, MD

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