Atlanta-Contrary to earlier data from a single-arm study, the addition of erlotinib (Tarceva) to the monoclonal antibody bevacizumab (Avastin) does not significantly delay disease progression in patients with metastatic renal cell carcinoma, according to data presented at the American Society of Clinical Oncology annual meeting. The new findings suggest that bevacizumab is responsible for increasing progression-free survival in this patient population.
"One of the issues in the past has been whether erlotinib was something that added to the activity," said first author Ronald M. Bukowski, MD, director of experimental therapeutics at the Cleveland Clinic Taussig Cancer Center. "I think the answer is 'no,' and it is clear that this drug, bevacizumab, is very well tolerated and is responsible for what has been reported in the past with this agent in combination with other drugs, such as erlotinib."
A total of 104 patients were enrolled at 20 sites between March 2004 and October 2004, with 53 receiving bevacizumab and 51, a combination of bevacizumab and erlotinib. The study was designed to allow patients to continue therapy for a maximum of 24 months, with a median follow-up of 9.8 months. Patients were treated from between 6 months to well over 18 to 20 months in some instances.
Study patients initially presented to the medical oncologist with the first diagnosis of metastatic disease. They were refractory either in the past or were found to have synchronous metastatic disease, and then were placed on the trial. All of the patients in the study were required to have previous nephrectomy. After having been treated surgically, they were receiving medical therapy because they were surgically unreceptive.
The primary measure of the trial was progression-free survival. Among the patients who received bevacizumab with placebo, the progression-free survival was 8.5 months, compared with 9.9 months among those who received the combination of bevacizumab and erlotinib, Dr Bukowski reported.
"In both arms, when you combine them, the progression-free survival was 8.6 months. In a patient group like this with no prior therapy, the expected progression-free survival would be in the range of 4 to 6 months," he said.
Dr. Bukowski interprets the outcome as demonstrating the effect of bevacizumab. Erlotinib had no contribution, except in terms of some moderate toxicities. Thus, in his opinion, this clearly validates the fact that bevacizumab does have activity in patients with untreated clear renal cell carcinoma.
"The long-term significance is that we have identified another agent, we believe, that is a useful treatment for renal cell carcinoma," he said. "We need to determine how to integrate this drug into the current treatment programs that are evolving for kidney cancer. Whether that is in combination with agents or as a single agent remains to be determined. We have to remember that this is a really well tolerated drug with very little toxicity. Most of the individuals on the study did very well in terms of their normal daily life patterns."