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Pazopanib
Thomas Hutson from the Baylor Sammons Cancer Center presented a poster on the interim results of a randomized discontinuation trial of Pazopanib in metastatic kidney cancer patients. Pazopanib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-kit. In other words, it blocks tumor growth and has anti-angiogenic activity.
The dosage was 800 mg of pazopanib taken orally once daily for 12 weeks. At the end of this cycle, the complete and partial responders were to be continued on treatment, but the patients with stable disease were to be randomized to either continue on pazopanib or be given a placebo. However, based on the positive activity of the drug, the randomization was discontinued, the patients on the placebo arm were crossed over to pazopanib, and the trial continued as a single-arm study.
225 patients were enrolled in the study. 68% of the patients were treatment-naïve, while 32% failed one prior treatment, mostly cytokine. The results, by independent review, at week 12 were.
| |
Patients (%) |
|
Partial Response |
61 (27%) |
|---|---|
|
Stable Disease |
104 (46%) |
|
Progressive Disease |
23 (10%) |
|
Withdrawn, adverse event, etc. |
37 (16%) |
The researchers stratified the patients in two groups: those who were treatment-naïve and those who had received prior systemic therapy. As can be seen below, the results were similar.
| |
No prior therapy |
Prior therapy |
| |
n = 154 |
n = 71 |
| |
Patients (%) |
Patients (%) |
|
Partial Response |
40 (26%) |
21 (30%) |
|---|---|---|
|
Stable Disease |
70(45%) |
34 (48%) |
|
Progressive Disease |
17 (11%) |
6 (8%) |
The only grade 3/4 event affecting close to 10% of the patients was hypertension, but significant adverse events affecting over 30% of the patients were diarrhea, hair color changes, nausea, and fatigue. Unlike for other targeted therapies, only 10% of the patients developed hand-foot syndrome. The most common laboratory toxicity was AST/ALT elevation of 50% (enzymes that monitor liver function), and 30% of the dose reductions were due to liver dysfunction.
47% of the patients remain on the study with a median duration of treatment for all patients of 28 weeks. A Phase 3 study has completed enrollment.
Reporter's comment: these are still preliminary results and do not include survival data. That said, the overall response is high and the side effects are tolerable. The word at ASCO was that Pazopanib will be approved by the FDA for kidney cancer some time in 2008.