Action to Cure Kidney Cancer

In a pre-surgical study, Eric Jonasch from MD Anderson in Houston, in an oral session, presented data on a Phase II presurgical study of the use of Avastin (bevacizumab) in untreated kidney cancer patients. Unlike the Cleveland Clinic study, the investigators' hypotheses in this trial were that Avastin therapy was safe and also prolonged time to progression. He also wanted to develop biomarkers from the treated tissue samples.

50 patients received 50 mg/kg of Avastin every 14 days for four cycles followed by nephrectomy if they had responding or stable disease and further Avastin. If they had progression but good performance status then they had a nephrectomy and were given other therapy. If they had progression but had poor performance status, they were not surgically treated and were given other therapy. The patients were basically intermediate risk (41) or poor risk (9) and at the time of their nephrectomy, i.e. after the Avastin treatment, 76% of them were classified as Stage III or Stage IV.

The progression-free survival was 11 months and overall survival was 25.4 months. The other results were as follows.

Primary Tumor - 45 evaluable patients

Metastatic Sites - 50 patients

Dr. Jonasch's conclusions were that a nephrectomy following Avastin treatment was safe, regression occurred in both the primary tumor and in the metastatic sites, and the clinical outcomes were similar to those obtained in patients who received post-nephrectomy treatment. With respect to biomarkers, he found that high expression of AMP-activated protein kinase (AMPK) is associated with a longer progression-free survival and trends toward a longer overall survival in Avastin-treated patients. But the latter observation requires further investigation due to the low number of cases and lack of statistical significance.

When asked by the session's moderator, Michael Atkins, about the benefit of this trial, Eric Jonasch pointed to the fact that oncologists do not know, upon diagnosis, how aggressive metastatic cancer will be. In this study, six patients did not undergo a nephrectomy after treatment with Avastin. If these patients had had prior nephrectomies, they may have undergone less systemic therapy like Avastin post-nephrectomy. So, he surmises that for these patients it was clinically beneficial to have received the Avastin upfront. In other words, neoadjuvant therapy given to metastatic patients is a method to pre-select those patients for nephrectomy. He advocated doing a randomized trial of patients diagnosed with advanced disease either having a nephrectomy or systemic therapy. Another question from the floor was why temsirolimus (Torisel) was not the therapy of choice since these were mostly patients with advanced metastatic disease. The answer was that temsirolimus was not available at the time of accrual to the trial.

The tumor response and survival data are difficult to compare to other studies since this is a single-institution trial of select patients. What is interesting about the study is that it seems to be a trend at MD Anderson to do pre-surgical studies on cancer patients to develop biomarkers for selection of future treatments. Donald Berry, a statistician at MD Anderson will be running a trial treating pre-surgical breast cancer patients with chemotherapy and experimental drugs to see which shrinks the tumor and analyzing the genetic makeup of the tumors that shrink and the women who respond to the treatment. He will then design a Phase III trial enrolling only those women who fit the same genetic profile of the responders to the original study. If, on the other hand, the original tumor had been removed and then the treatment been given, it would have taken five to ten years to ascertain whether or not the therapy was successful.

We'll see if this is a future trend in kidney cancer treatment. As for the fear of leaving the tumor in the kidney, it's not the primary tumor that will kill you but the metastases.

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