The oral angiogenesis inhibitor pazopanib (Votrient) more than doubled progression-free survival versus placebo in a randomized, phase III trial of patients with advanced renal cell carcinoma.
Rome-The oral angiogenesis inhibitor pazopanib (Votrient) more than doubled progression-free survival versus placebo in a randomized, phase III trial of patients with advanced renal cell carcinoma.
Among 435 patients randomly assigned 2:1 to receive either pazopanib, 800 mg once daily, or placebo, progression-free survival was 9.2 months in the pazopanib group and 4.2 months in the placebo arm (p<.0001).
The difference was even greater in the 233 treatment-naïve patients (11.1 vs. 2.8 months, p<.0001), and was maintained among the 202 patients previously treated with cytokine therapy (7.4 vs. 4.2 months, p<.001).
"Physicians should know that there is another option for the treatment of patients with advanced RCC," said lead author Cora Sternberg, MD, chief of medical oncology at San Camillo and Forlanini hospitals in Rome. "Treatment has improved in the past few years with the introduction of targeted therapies, but advanced RCC remains a challenging disease."
The FDA approved pazopanib for treatment of advanced RCC in October 2009. The agent works by inhibiting endothelial growth factors (VEGFR-1, 2, and 3) and other tyrosine kinases (PDGFR-α, PDGFR-β, and c-kit).
The objective response rate in the trial was 30% with pazopanib, compared with 3% with placebo (p<.001). Median duration of response was 1 year.
Dr. Sternberg said pazopanib is currently being evaluated in comparison with other vascular endothelial growth factor inhibitors. An ongoing, phase III, open-label trial known as COMPARZ, for instance, is examining pazopanib versus sunitinib (Sutent) in 876 patients with metastatic clear-cell RCC and no prior treatment. In addition, another trial, known as PISCES, will address patient preferences between the two drugs.
Drug found safe, well tolerated
Among patients in her group's pazopanib investigation, Dr. Sternberg said the medicine was "very well tolerated" and that its safety has been well characterized. The most common side effects were diarrhea (52%), hypertension (40%), hair color changes (38%), nausea (26%), weight loss (22%), and vomiting (21%).
"The side effects are what one might expect with this class of agents," she said.
Dr. Sternberg noted that the trial was the first placebo-controlled, phase III pazopanib study to include both treatment-naïve and cytokine-pretreated patients and show a significant improvement in progression-free survival in both groups.
She said the study had been intended only for cytokine-refractory patients, "but was rapidly amended after only a few patients were entered, as there was great interest for patients who were not cytokine-pretreated to participate."
Three of the study's co-authors are employees of GlaxoSmithKline.