Bevacizumab Added to Kidney Cancer Therapy Extends Survival

Allison Gandey

June 13, 2007

June 13, 2007 (Chicago) — A new trial shows that adding bevacizumab ( Avastin, Genentech) to interferon nearly doubles progression-free survival in patients with renal cell carcinoma. "When you look at the data, the combination is better than interferon alone," lead investigator Bernard Escudier, MD, head of the immunotherapy unit at the Gustave Roussy Institute, in Villejuif, France, told Medscape. "In my opinion, it's at least as safe and well tolerated as interferon alone," he said. The findings were presented during the plenary session here at the 43rd annual meeting of the American Society of Clinical Oncology.

"This is an important and well-conducted study by a distinguished colleague," Ronald Bukowski, MD, director of the experimental therapeutics program at the Cleveland Clinic Taussig Cancer Center, in Ohio, said during the discussion period following the presentation.

During an interview, Dr. Escudier said he was somewhat surprised by the results. "We did not expect to find such a big difference between treatments. We had anticipated about a 30% improvement and yet we saw a doubling of progression-free survival. That was unexpected."

Dean Bajorin, MD, from Memorial Sloan-Kettering Cancer Center, in New York, and moderator of a press conference outlining the findings, called the progression-free survival data "striking," and he commended this group and others for moving the standard of care for kidney cancer forward.

Until recently, there were few options for patients with renal cell carcinoma. In the past 18 months, however, 2 targeted therapies have shown efficacy and received approval from the US Food and Drug Administration: sorafenib ( Nexavar, Onyx Pharmaceuticals) and sunitinib ( Sutent, Pfizer). "We're in a very exciting time in kidney cancer research with a number of new targeted therapies becoming available," Dr. Escudier told reporters.

Bevacizumab is currently approved for the treatment of advanced colorectal and nonsmall cell lung cancers. It is a monoclonal antibody that inhibits tumor angiogenesis by targeting vascular endothelial growth factor. In the current analysis, known as the AVOREN trial, investigators studied the effect of adding bevacizumab to interferon ( Roferon, Roche) as a first-line treatment for advanced kidney cancer.

In this randomized, double-blind, placebo-controlled, phase 3 study, the European researchers looked at nephrectomized patients with renal cell carcinoma. They received interferon alpha 2a plus bevacizumab at a dose of 10 mg/kg every 2 weeks or placebo until disease progression.

Tumor Response

Response Interferon with Placebo (n=289) Interferon with Bevacizumab (n=306)
Overall Response Rate (%) 13 31
  • Complete Response

2 1
  • Partial Response

11 30
Median Duration of Response (mo) 11 13
Median Duration of Stable Disease (mo) 7 10



Progression-Free Survival

Outcome Interferon with Placebo (n=289) Interferon with Bevacizumab (n=306) Hazard Ratio P
Median (mo) 5.4 10.2 0.63 <.0001



Overview of Adverse Events

Outcome Interferon with Placebo (n=304) Interferon with Bevacizumab (n=337)
Grade ≥ 3 Adverse Event (%) 45 60
  • Serious Adverse Event

16 29
Discontinuation Due to Toxicity (%)    
  • Any Study Drug

12 28
  • Bevacizumab or Placebo

6 19
  • Interferon

12 23
Death Not Due to Progressive Disease 2 2



Need More Long-Term Toxicity Data and Information on Grade 3 and 4 Adverse Events

Discussing the findings, Dr. Bukowski pointed to a number of limitations to the trial. He suggested that a third study arm, a bevacizumab monotherapy group, would have been useful. "Previous phase 2 data of bevacizumab suggest the benefit seen is predominantly due to this agent. A monotherapy comparator arm would therefore have been helpful in determining this," he said.

Dr. Bukowski also noted that the data are preliminary and additional information on overall toxicity is needed, including on long-term effects and grade 3 and 4 adverse events.

With new alternatives available, interferon is no longer considered the standard of care for most patients with kidney cancer. Future studies are likely to test bevacizumab as a single agent for first-line treatment of renal cell carcinoma by comparing it head to head with sorafenib and sunitinib. Additional trials are also anticipated to test bevacizumab in combination with these products and with the recently approved drug temsirolimus ( Torisel, Wyeth).

"The future lies not in the comparison of these drugs," Dr. Escudier told Medscape, "but in the combinations of these products."

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 3. Presented June 4, 2007.

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