Presurgical Feasibility of Bevacizumab for Nephrectomy-Eligible, Treatment-Naïve Patients with Metastatic Renal Cell Carcinoma

ROBERT A FIGLIN, MD:
The manuscript by Eric Jonasch summarizes the MD Anderson experience with presurgical bevacizumab in patients with metastatic kidney cancer who had their primary tumors intact. They report on 52 patients with clear cell carcinoma, who were enrolled during a three-year period, in whom they evaluated the benefit of bevacizumab for eight weeks prior to surgical resection. This presurgical approach is primarily one for the clinical research setting and should not be performed outside of a clinical trial.

The results of this trial as reported by Jonasch demonstrate several points. Approximately 18 percent of the patients had Memorial Sloan-Kettering Cancer Center (MSKCC) poor-risk disease, and that’s important because we do not have evidence that bevacizumab has activity in these patients. Of the remaining population, 82 percent of the patients had intermediate-risk renal cell carcinoma — most of them with T3 to T4 disease. Ten patients had pathologic T1 disease, raising the question, What is the role for neoadjuvant or presurgical treatment for a patient with clinical T1 disease?

The authors demonstrated that they could administer bevacizumab safely, although the response rates were modest as expected from bevacizumab alone.

They observed little in the way of benefit with respect to the primary tumor, although the waterfall plot demonstrated that 52 percent had decreases in tumor size. Some of the patients’ metastatic disease did have a reduction with one complete response of metastatic disease and 10 percent partial remissions.

Of note, the side effects were significant, remembering that many of these patients could have otherwise gone on to receive definitive surgical resection or systemic therapy for the treatment of their metastatic disease. The wound-healing delay that occurred in some patients is worrisome.

In fact, when one evaluates the data, three patients in the bevacizumab-alone group had delayed wound healing or dehiscence and two patients in the bevacizumab and erlotinib group died, which was not thought to be associated with the study drugs. So these patients likely had poor prognoses, and receiving this specific systemic therapy prior to definitive surgical resection might have not been the appropriate choice. Although the authors do not believe that the study drugs were associated with the deaths, they are still perioperative deaths in two out of 23 patients dying in close proximity to their surgery, which is a high mortality rate of 10 percent.

In summary, although bevacizumab can be administered safely in a presurgical setting with some clinical benefit — with respect to a modest reduction in the size of metastatic disease and in the size of the primary tumor — that has to be counterbalanced by wound-healing delays, perioperative morbidity, mortality and the as-yet-defined benefit of neoadjuvant therapies as opposed to treating definitively with surgical resection followed by systemic therapy or the appropriate systemic therapy alone.

Other clinical trials are investigating tyrosine kinase inhibitors (TKIs) prior to surgical resection with either sunitinib or sorafenib, but again, in the clinical setting for the practicing physician, presurgical treatment prior to surgical resection should be reserved for participation in a prospective, IRB-reviewed clinical trial and not as part of a standard regimen.

Dr Figlin is Acting Cancer Center Director, Arthur and Rosalie Kaplan Professor of Medical Oncology as well as Chair of the Division of Medical Oncology and Experimental Therapeutics at the City of Hope National Medical Center/Beckman Research Institute in addition to Associate Director for Clinical Research at the City of Hope Comprehensive Cancer Center in Duarte, California.