For bevacizumab (Avastin), as for all targeted agents, there is a critical need to identify likely responders as well as patients at risk for serious toxicities, agreed Daniela Matei, MD, of the Indiana University Melvin and Bren Simon Cancer Center, and session moderator Daniel F. Hayes, MD, of the University of Michigan.

A recent cost-effectiveness analysis of Gynecologic Oncology Group (GOG) 218 drove this point home.¹ Investigators determined that for the 600-patient trial in advanced disease, the cost of chemotherapy alone (carboplatin/paclitaxel) was $2.5 million, rising to $21.4 million with the addition of bevacizumab, and further to $78.3 million when bevacizumab was continued as maintenance. While progression-free survival also improved exponentially, from a median of 10, to 21, to 31 months, respectively, the addition of bevacizumab was not cost-effective, the authors maintained.

In the adjuvant setting, the data are not convincing, Dr. Matei noted. “I have been underwhelmed, and I personally don’t prescribe it upfront outside of a clinical trial. For recurrence, perhaps the magnitude of benefit is greater. Certainly the trend for overall survival is there, but we have to take into account the potential toxicities when determining how to use the drug. I do think bevacizumab is active in ovarian cancer,” she acknowledged. “But when and how to give it, and to whom, for the best outcomes—those issues are still up in the air.”

Duration of Therapy

Dr. Hayes said he is also troubled by not knowing how best to give bevacizumab, largely because the target is vague. But the even bigger issue, he said, is duration. “All the trials—in colon, lung, breast, and ovarian cancers—have suggested that as long as you give bevacizumab you continue to see benefit. You quit, and the curves collapse. Universally, the curves come together, suggesting we need to keep giving it forever,” he remarked.

“But we cannot afford to give bevacizumab to every patient, and it’s a disgrace that we have not yet learned who the drug works in and who will have life-threatening toxicity,” he commented. “Unfortunately for our patients, we may be on the verge of throwing the baby out with the bathwater.” ■

Disclosure: Dr. Hayes holds stock in Oncimmune, LLC, has served as a consultant for Chugai Pharmaceuticals and Biomarker Strategies, and has received research funding from Pfizer, Novartis, and Veridex (Johnson & Johnson). Dr Matei has received consulting fees from Genentech.

Reference

1. Cohn DE, Kim KH, Resnick KE, et al: At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer: A cost-effectiveness analysis. J Clin Oncol 29:1247-1251, 2011.