On Friday, the FDA granted accelerated approval to
bevacizumab in combination with paclitaxel for the treatment of metastatic
breast cancer. The decision, which has surprised many, goes against the
recommendation of the Oncologic Drugs Advisory Committee who in December
recommended against approval of the drug for the first-line treatment of breast
Bevacizumab (Avastin, Genentech) was approved for
advanced breast cancer under the FDA’s accelerated approval program, which
allows the FDA to approve products for cancer or other life-threatening
diseases based on initial positive clinical data.
The approval was based on findings from the E2100 study
that found improvement in progression-free survival but not overall survival.
As a result, it has sparked some speculation among the medical community that
the FDA has lowered its standards for the approval of cancer drugs.
“To say that the FDA has never approved a drug in
the first-line setting without documented overall survival advantage is simply
not true. Neither gemcitabine (Gemzar, Eli Lilly and Company) nor trastuzumab
(Herceptin, Genentech) had an overall survival advantage at the time they were
first approved (later follow-up did find a survival advantage). In addition,
the two most recent drugs approved in breast cancer for patients who had
received previous chemotherapy did not have an overall survival advantage. They
were approved on much more modest improvements in progression-free
survival,” Kathy D. Miller, MD, lead investigator on the E2100
study, told HemOnc Today.
Results of E2100—an international, multi-center,
randomized and controlled study—showed that bevacizumab in combination
with paclitaxel resulted in a 5.5-month increase in median progression-free
survival compared with those patients treated with paclitaxel alone; however,
these patients also had an increased rate of grade-3 to -5 adverse events.
“This [approval] gives patients with HER2-negative
disease a new and very powerful option for combination with paclitaxel as their
first chemotherapy for metastatic disease. These are patients who typically
have a good quality of life with, typically, few symptoms of their disease, and
being able to prolong that period of time for twice as long as we can with
chemotherapy alone is a huge advantage for those patients,” said Miller,
who is also an associate professor at Indiana University School of Medicine.
Before full approval is granted, the FDA is expected to
review a summary of the results from the phase-3 AVADO and RIBBON 1 trials;
complete data will be available late this year. – by Leah Lawrence and
Stacey L. Adams
The FDA made the right decision with accelerated approval of bevacizumab
for advanced breast cancer, showing their commitment to the well-being of
patients. This will also advance the national research agenda in breast cancer,
providing support for the ongoing Intergroup trial testing the value of
bevacizumab in high-risk early breast cancer.
– Nancy Davidson, MD
HemOnc Today Breast Cancer section editor