• Oncology Clinical Trials
• Gastrointestinal Cancers

The AVOREN trial was conducted to compare interferon alone with interferon plus bevacizumab for the treatment of metastatic renal cell carcinoma (RCC). The findings of the trial represent an important step in the recent advances in the treatment of RCC.

“In this placebo-controlled study, the addition of bevacizumab to interferon results in clinically important and statistically significant improvement in progression-free survival and tumor response,” said Bernard Escudier, MD, Institut Gustave Roussy, France, who reported the findings of the study. The antiangiogenic agent, which targets vascular endothelial growth factor (VEGF), joins two other VEGF inhibitors, sunitinib and sorafenib, as effective agents for metastatic RCC.

Dr. Escudier explained that analysis of tissue samples from several different types of cancer has demonstrated that RCC is associated with the greatest expression of VEGF. In a phase 2 trial, bevacizumab (10 mg/kg) significantly improved the time to progression after failure of cytokine therapy.

The multicenter trial included 649 patients with advanced RCC who had undergone nephrectomy. The patients were randomly assigned to treatment with interferon (9 MIU, subcutaneously, three times per week) plus bevacizumab (10 mg/kg, intravenously, every two weeks; n=322) or the same dose of interferon plus placebo (n=327). The primary endpoint was progression-free survival (PFS).

Dr. Escudier reported that tumor response and PFS were significantly better in the interferon plus bevacizumab arm than in the interferon alone arm. In the 595 patients who had measurable disease, tumor response occurred in 31% of patients who received the combination therapy and in 13% of patients who received interferon alone (p <0.0001). The median PFS was 10.2 months for the combination therapy and 5.4 months for interferon alone.

Dr. Escudier explained that PFS was also evaluated in patient subgroups stratified according to Motzer score. For patients who had a favorable or intermediate Motzer score, the PFS was significantly better for interferon plus bevacizumab than for interferon alone. However, for patients with a poor score, there was no significant difference between the two treatment groups (Table 1).

At the time of interim analysis of overall survival, 251 of 450 scheduled events had occurred. The median overall survival had not been reached for the interferon plus bevacizumab arm and was 19.8 months for the interferon alone arm.

Interferon plus bevacizumab was well tolerated. The rate of grade 3 or 4 adverse events was 60% for the combination therapy arm and 45% for the interferon alone arm. The most common grade 3 or 4 adverse event was fatigue/asthenia/malaise, which occurred more frequently among patients who received interferon plus bevacizumab (23% vs 15%).

• © 2007 MD Conference Express