Quality vs. Quantity: Who’s to Say?

Is quantity of life more valuable than quality of life, and who should be the judge? That seems to be the crux of the dissension between the Food and Drug Administration and the breast cancer guideline panel of the National Comprehensive Cancer Network (NCCN) regarding the use of bevacizumab (Avastin, Genentech) for the treatment of HER2-negative metastatic breast cancer.

In December of last year, the FDA announced that it would be removing the breast cancer indication for the drug, which was initially approved under the agency’s accelerated approval program in 2008 based on promising findings of its use in combination with paclitaxel (Taxol) in the E2100 clinical trial. Following a subsequent review of the trial data and information from additional clinical trials provided by Genentech, the FDA deemed the small increase in progression-free survival in the absence of an overall survival benefit to be outweighed by the risks associated with the drug, and has begun the process of removing the indication.

Although the FDA action would not preclude off-label use of the drug in breast cancer patients, it would effectively prevent it by giving payers a reason not to finance it. As such, Genentech is appealing the decision and appears to have the support of the NCCN, which is retaining bevacizumab in the updated treatment recommendations announced over the weekend at the organization’s annual conference in Hollywood, Florida.

Dr. Robert W. Carlson. Image courtesy of Stanford University.

After multiple “marathon” meetings to discuss the FDA action, the 26-member NCCN breast cancer guideline panel decided unanimously to reaffirm its existing recommendation for bevacizumab in combination with paclitaxel as a therapeutic option for metastatic breast cancer, panel chair Dr. Robert W. Carlson announced at the conference. “The data observed in the [E2100 clinical trial] really had not changed from its approval previously, and we thought, if the data were compelling 2 years ago, why isn’t it compelling enough today?”

A revised footnote accompanies the panel’s recommendation: “Randomized clinical trials in metastatic breast cancer document that the addition of bevacizumab to some first- or second-line chemotherapy agents modestly improves time to progression and response rates but does not improve overall survival. The time-to-progression impact may vary among cytotoxic agents and appears greatest with bevacizumab in combination with weekly paclitaxel.”

Dr. Carlson, of Stanford University (Palo Alto, CA) was not dismissive of the toxicities associated with bevacizumab, but reiterated the panel sentiment that the progression-free survival benefit is a quality of life measure that should not be overlooked. “Progression-free survival is an important end point in the adjuvant setting. If it means the difference between 5 months with the disease under control vs. 5 months of disease progression, there is value in that.”

Dr. Carlson disclosed receiving grant and research support from AstraZeneca Pharmaceuticals LP, Genentech, Inc., Pfizer Inc., and Sanofi-aventis US.

—Diana Mahoney


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Filed under Drug And Device Safety, Family Medicine, Health Policy, IMNG, Oncology, Primary care

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