Bevacizumab offered no OS benefit in metastatic breast cancer

Issue: August 10, 2012

The addition of bevacizumab to chemotherapy offered slightly improved PFS but did not extend OS among patients with metastatic breast cancer, according to results of a systematic review.

Perspective from Douglas Yee, MD

The FDA approved bevacizumab (Avastin, Genentech) for use in metastatic breast cancer patients in 2008 under its accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval.

In November 2011, the FDA revoked its approval of the breast cancer indication because of concerns about side effects, as well as a lack of evidence that patients who took the drug lived longer or had improved quality of life compared with those who received chemotherapy alone. Bevacizumab remains an approved treatment in the United States for certain types of colon, kidney, lung and brain cancers. It also is approved for first-line treatment of metastatic breast cancer in Europe.

Anna Dorothea Wagner, a researcher with the Fondation du Centre Pluridisciplinaire d’Oncologie at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and colleagues conducted this study to evaluate the clinical value of bevacizumab in combination with other established chemotherapy drugs in patients with metastatic breast cancer.

The researchers collected data from seven randomized controlled trials that involved 4,032 patients.

Patients who received bevacizumab with first-line chemotherapy experienced significantly improved PFS (HR=0.67; 95% CI, 0.61-0.73) and response rate vs. patients who underwent chemotherapy alone.

Patients who received bevacizumab with second-line chemotherapy also experienced longer PFS (HR=0.85; 95% CI, 0.73-0.98) and improved response rate compared with patients who underwent chemotherapy alone.

The addition of bevacizumab increased the time to tumor progression or death by between 1 and 6 months, the researchers found. The magnitude of the benefit depended on the type of chemotherapy used.

However, bevacizumab did not increase OS when added to first-line (HR=0.93; 95% CI, 0.84-1.04) or second-line chemotherapy (HR=0.98; 95% CI, 0.83-1.16).

“At best, adding bevacizumab to standard chemotherapy appears to offer a modest benefit for those with metastatic breast cancer,” Wagner said in a press release. “Whether it can truly be of benefit to the patient is debatable, because it only briefly prolongs progression of the disease.”

Reference:

Wagner AD. Cochrane Database Syst Rev. 2012;7:1-84.

Perspective

Douglas Yee, MD

I think a major issue is the relative lack of predictive biomarkers of benefit. That has been a longstanding problem with all of the anti-angiogenic agents. The biology of vascular endothelial growth factor is pretty complicated, and it is hindering the ability to come up with a specific biomarker that would identify benefit. If you think of the more exciting drugs that have been approved in the previous months or years, you would notice that everything has been developed with a companion biomarker. It is getting harder and harder to develop an agent without that biomarker.

Douglas Yee, MD

HemOnc Today Editorial Board Member

Disclosures: Dr. Yee reports no relevant financial disclosures.