(HealthDay News) – The potent, selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, tivozanib, demonstrates antitumor activity and is well tolerated in patients with advanced/metastatic renal cell carcinoma (RCC).
Dmitry A. Nosov, MD, PhD, of the Blokhin Oncology Research Center in Moscow, and colleagues conducted a Phase 2 randomized discontinuation trial (RDT) involving 272 patients with advanced or metastatic RCC to evaluate the antitumor activity and safety of tivozanib. Patients were given 1.5mg/d orally for 16 weeks, where one cycle was defined as three treatment weeks followed by a one-week break. During the first open-label phase of the trial, patients who experienced >25% tumor shrinkage continued to take tivozanib, while those with <25% shrinkage progressed to the second 12-week, double-blind phase and were randomized to receive either tivozanib or placebo. If patients experienced >25% tumor growth, they were discontinued from the trial. Safety, objective response rate (ORR) at 16 weeks, and percentage of patients who were progression free after 12 weeks of double-blind treatment were primary end points, and progression-free survival was a secondary end point.
The researchers found that, overall, 83% of participants had tumors with clear-cell histology, 73% had undergone nephrectomy, and 54% were treatment naive. In the 16-week open-label phase, the ORR was 18%. Among the 118 patients randomized to treatment with tivozanib or placebo, a statistically significant between-group difference in the percentage of patients who remained progression free after 12 weeks was observed (49 and 21%, respectively). Grade 3 and 4 hypertension was the most common treatment-related adverse event.
“Results from this RDT demonstrated promising activity and an acceptable safety and tolerability profile for tivozanib in advanced/metastatic RCC,” the authors write.
The study was supported by AVEO Pharmaceuticals; several authors disclosed financial relationships (including employment) with AVEO.