The most widely used anti-cancer drug, Avastin, should not be used to treat breast cancer, the US Food and Drug Administration (FDA) recently decided. This drug is not effective enough to justify the risk of serious side effects.
The decision was made five months after the FDA’s advisory committee recommended the agency to withdraw its approval of Avastin’s use in breast cancer patients. While clinical trials have for years fueled doubts about the drug’s usefulness in fighting the cancer, FDA commissioner Margaret A. Hamburg admits that the decision was not easy, as many women and doctors had high hopes for the drug and lobbied to maintain its approval. “It was a difficult choice,” said Hamburg. “Sometimes, despite the high hopes of scientists, doctors, patients, industry, and even the FDA itself, rigorous testing results have been disappointing.
Avastin will remain on the market and will continue to be used against other types of cancer – such as lung, kidney and colon cancer – where the benefits outweigh the risks, Hamburg added. As long as the drug is available, doctors in the US will be able to prescribe it to patients with breast cancer, except off-label, which means that insurance companies will not reimburse it.
Avastin, one of the best-selling anti-cancer drugs, is a biological antibody that blocks the blood supply to a tumor and reduces its vascularization and growth. Despite its effectiveness, it can cause serious side effects, including heart attack and stroke. Therapy with this drug is one of the most expensive anti-cancer therapies, in the US it costs over 50. dollars a year. The FDA approved the use of Avastin for the treatment of breast cancer with metastasis to other organs in 2008, when the New England Journal of Medicine published the results of a study that showed that when combined with a chemotherapy drug, it stops disease progression and extends patients’ lives by six months compared to the group that used only chemotherapy. It was the first formulation approved through an accelerated approval program that allowed the drug to be used while it was still being tested for its safety and efficacy. The permit was already controversial then. The FDA’s advisory panel, which had voted on the issue a few months earlier, voted against the drug’s approval by a vote of 5-4. Two independent studies have shown that Avastin appears to slow the growth of breast cancer, but it does not extend the life of patients. The FDA, which was closely monitoring new data that either confirm or undermine the drug’s benefits, decided in December 2010 to withdraw approval for Avastin’s use in the fight against breast cancer, but its manufacturer, Genentech, contested the agency’s ruling. Drugs that are approved at an accelerated pace require rigorous follow-up, explains Hamburg. In the case of accelerated approval programs, consent withdrawal is part of the process, the researcher says.
The doubts surrounding Avastin are nothing new, and the FDA’s decision to withdraw the recommendation has surprised few experts. “The drug does not improve quality of life,” confirms oncologist Joanne Mortimer, director of the Women’s Cancer Program at City of Hope Clinic in Duarte, California, who participated in two of the three FDA panels on the use of Avastin in breast cancer treatment. – Yes, the cancer is under control for a while, but the risk is disproportionate. Studies have shown that patients with advanced breast cancer who take Avastin have a significantly increased risk of dying from a stroke or heart attack. In addition, the drug has been proven to raise blood pressure and increase the risk of heart failure. Serious haemorrhage was five times more common in Avastin users than in those confined to chemotherapy alone. The hope that Avastin can extend the lives of patients with advanced breast cancer was awakened by a study, the results of which were published in 2007 in the New England Journal of Medicine. Researchers have noticed that in women who take the drug in combination with Paclitaxel chemotherapy, the development of the disease is stopped for an average of 11,8 months. For comparison, chemotherapy alone halted tumor progression for an average of 5,9 months. But even this study did not show that patients taking Avastin live longer, said Dr. Kerin Adelson, an oncologist at Mount Sinai School of Medicine in New York. Subsequent tests definitely confirmed that Avastin does not extend life, and moreover, highlighted the risks associated with taking this drug, adds Adelson. (One of her breast cancer patients who was treated with Avastin had a major stroke). – Many drugs extend the time of cancer development, but do not extend the life of patients – says the doctor. – This is the situation with Avastin.
In 2010, the drug made about $ 3,5 billion in profit, but this year, since the FDA’s advisory committee announced the withdrawal of the recommendation, sales fell. There are no exact data on how many breast cancer patients have been treated with this medicine, but doctors say it was commonly prescribed for people who had metastatic disease. Genentech, the San Francisco-based company that produces Avastin, do not hide their disappointment with the FDA’s decision, but announce that the third phase of clinical trials will soon begin, which will further determine how the drug works in combination with Paclitaxel. An additional study is also planned to identify biomarkers to determine if the drug may be of benefit for specific patients. Some scientists still believe that the drug may benefit certain groups of women with breast cancer, such as patients with triple negative cancer, which is an especially dangerous form of cancer because it grows quickly and spreads quickly.
“This is not the end of Avastin, even for breast cancer patients,” said Dr. Neal Meropol, hematologist and oncologist at the University Hospitals Case Medical Center in Cleveland, chairman of the research group at the American Society of Clinical Oncology. – It is very likely that Avastin will be of great benefit to some groups of patients. Our task is to determine which breast cancer patients can receive therapy with this preparation. Meropol, however, stressed that he agreed with the FDA’s decision and praised the agency’s diligence in investigating the matter. “I believe the FDA made the right decision, based on scientific data as well as the opinions of experts, patients and drug makers,” he said. (…)
Some breast cancer associations have had doubts about Avastin’s effectiveness before, despite its enormous popularity. “Our position was clear from the outset: this drug should not be approved for use in the treatment of breast cancer,” says Fran Visco, chairman of the Washington National Breast Cancer Coalition, which supports the decision.
According to Mortiner, patients should not worry about Avastin’s withdrawal from the breast cancer arsenal, because they always have chemotherapy. – There are better and better drugs to fight breast cancer – he says.
Text: Shari Roan