Action to Cure Kidney Cancer

Robert Motzer made an oral presentation of the updated results of a multi-institutional, Phase 3 trial of Sutent versus Interferon in a first-line setting. The original Phase 3 trial, presented at ASCO in 2006, showed superiority of Sutent over Interferon. This was a 750-patient trial, with all patients having clear cell pathology. 375 patients (pts) were randomized to each arm of the trial.

Sutent versus Interferon Results

The numbers remaining on therapy were as of the data cutoff date, February 2007. The objective response figures were certified by independent assessment, but a number of these patients later progressed. The PFS figures are the same as given by Dr. Motzer last year, and they led the oncologists both at the 2006 ASCO and at this year's conference to proclaim Sutent as the preferred choice for first-line targeted therapy.

Dr. Motzer stratified the PFS results by risk status, which predicts overall survival.

Progression-Free Survival by Risk Group

Reporter's Comment: This doesn't tell us anything new about Sutent, but allows us to compare the Sutent statistics with data reported by Bernard Escudier for the Avastin/Interferon trial at this year's ASCO - see Avastin and Interferon.

Comparison of Sutent and Avastin/Interferon

The Avastin results are the best ever gotten for this drug in kidney cancer, while Sutent has proven to be an active targeted therapy in renal cell. Nevertheless, as one can see, the Escudier trial results make Avastin a player in kidney cancer treatment, possibly in combination with Sutent, and oncologists at ASCO recommended it as an option for first-line treatment for kidney cancer. It will be interesting to see if results of future Avastin trials, especially as a monotherapy, confirm the Avastin/Interferon results.

Dr. Motzer spent the next part of his lecture talking about a statistical tool that he developed that, given certain patient characteristics, predicts the probability of an individual patient who is on Sutent therapy being disease-free in 12-months, i.e. the probability of progression-free survival (PFS) at 12-months. Dr. Motzer went through a number of slides finally arriving at what is called a nomogram, which is a chart that listed seven factors, each having point values that add up to a total probability of PFS at 12-months. Some of Dr. Motzer's factors are corrected calcium level, number of metastatic sites, prior nephrectomy, time from diagnosis to treatment, physical status of the patient, etc.

However, Dr. Primo Lara of UC Davis, the discussant for Dr. Motzer's talk, said that Dr. Motzer was confounding prognostic versus predictive biomarkers. Dr. Lara said that prognostic biomarkers "reflect the natural history of the disease independent of treatment received" whereas predictive biomarkers, which do not yet exist for kidney cancer, but do for other cancers, "reflect the impact of therapeutic intervention". In other words, the predictive biomarkers indicate the probability of the therapy working for a patient given that patient's biomarker profile.

Dr. Motzer's biomarker's were of the prognostic kind. For example, the fewer the metastatic sites, the higher the probability of a better prognosis no matter what the treatment. Oncologists are experimenting with predictive markers with respect to Interleukin-2 treatment. The Select trial will test responsiveness to treatment by IL-2 for patients who have clear cell pathology with alveolar features and high carbonic anhydrase expression. The presence of these factors is hypothesized to yield a favorable outcome to treatment of metastatic RCC patients with IL-2. However, no such biomarkers currently exist for the targeted therapy treatments, and Dr. Lara called upon the cancer community to develop, in the oncoming combination trials, molecular biomarkers that can have predictive value for resistance to therapy and for early progression.

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