On November 18th the FDA officially revoked Avastin's breast cancer label in the United States. For those who have been following the Avastin breast cancer debate this decision, however unsurprising, has been met with mixed opinion and on the side of patients in particular mixed emotion.

The Avastin Saga in breast cancer began in earnest in mid-2010 when the Oncology Drug's Advisory Committee (OCAC) recommended that the FDA remove Avastin's label in HER-2 negative breast cancer because it does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. This recommendation was made based on a full review of three Phase III studies; E2100, AVADO and RIBBON-1 which evaluated Avastin plus chemotherapy in first-line metastatic breast cancer. Although all three studies demonstrated a statistically significant improvement in progression-free survival (PFS) (the primary endpoint in all three studies), AVADO and RIBBON-1 failed to emulate the magnitude of PFS benefit (5.5 months) demonstrated in the original Avastin plus paclitaxel E2100 study, the results of which led to Avastin's conditional approval in 2008.

The process to remove Avastin's conditional approval has been a lengthy and heavily debated one. After the FDA announced in December 2010 that it intended removing Avastin's label Genentech launched an official appeal which culminated in a two-day hearing in June 2010. After intensive and at times emotive debate, as well as protests from breast cancer patients and support groups the appeal failed and an advisory committee to the FDA voted to uphold the decision to revoke Avastin's label. Almost one year after the FDA announced its original decision, the FDA commissioner Margaret Hamburg published in a 69-page memorandum this month that the process has been finalized.

Many believe that the FDA's decision on Avastin will help to uphold the integrity of the accelerated approval program which allowed its approval in the first place. However, this is likely to come as little consolation to breast cancer patients, who after hearing of countless success stories of Avastin in breast cancer may feel that a valuable therapeutic option has been denied them. Perhaps even more confusing to patients is that Avastin plus paclitaxel is still recommended by the National Cancer Comprehensive Network (NCCN) guidelines, a recommendation that was reaffirmed in October 2010.

Adding to the confusion is the European Medicines Agency's contrasting stance on Avastin in breast cancer. After reviewing the same Avastin data the European Medicines Agency reaffirmed approval of the drug in combination with paclitaxel in December 2010. Although the European Medicines Agency no longer recommends Avastin in combination with docetaxel they have since extended Avastin's label to allow it use in combination with Xeloda for first-line metastatic patients who are ineligible for treatment with a taxane or anthracycline. In an additional twist the Japanese Regulatory Authority approved Avastin in combination with paclitaxel as a first-line treatment for metastatic HER2-negative breast cancer in September 2011. Notably, the United Kingdom's National Institute of Clinical Excellence (NICE) never recommended Avastin as a treatment for breast cancer patients.

Breast cancer patients in the United States may still be prescribed Avastin off-label and government officials have said that Medicare will continue to provide coverage though they intend to monitor the issue and evaluate coverage options. For the time being at least Avastin is also still covered by third-party health insurers, although some including the 3.3 million member health plan Blue Shield have already announced that they will no longer cover the cost of Avastin for breast cancer patients.

Prescribing of Avastin for breast cancer has already declined dramatically in the United States and is likely to fall even further now that the FDA's decision is finalized. Even in Europe where the agent has retained its label prescribing has declined due to reimbursement restrictions and more discerning prescribing by oncologists. Avastin's hope of recovery to its original glory in breast cancer now relies on the identification of a predictive biomarker to identify patient most likely to respond to treatment. Genentech have pledged to carry out an additional Phase III study of Avastin in plus paclitaxel in first-line metastatic breast cancer to evaluate a potential biomarker candidate. However, considering the huge amount of research that has been invested into finding a biomarker for Avastin, one can't help but wonder, if there is such a biomarker why hasn't is already been found it.

Pivoting a product launch during the pandemic

View Now