Unique breast cancer drug nearing approval
11 SEP1998 Scientists have known for years that some cases of breast cancer are driven by a flaw in a normal body communication system. These cancer cells have too many growth factor receptors, and they receive an abnormal stimulus from growth factor molecules in the blood.
The result of this signaling system gone awry is too much cell division -- cancer.
The receptor in question is called HER2 (human epithelial growth factor receptor). Based on promising clinical studies, on Sept. 5, a Food and Drug Administration panel recommended approval for a new drug called Herceptin.
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This drug blocks HER2 and prevents it from receiving the signal from growth factor.
Herceptin could receive full FDA approval as early as Nov. 4.
The new therapy is only suitable for the 25 to 30 percent of breast cancers that produce excess HER2 molecules. The FDA is expected to permit Herceptin to be used alone or in combination with taxol, a drug derived from the yew tree.
Herceptin is a monoclonal antibody, meaning that it contains innumerable copies of an antibody -- a molecule designed to attach to one specific protein in the body.
Trying to interfere with an errant signaling mechanism is a radical departure from existing cancer treatments. Chemotherapy and radiation both target fast-growing cells, but that harms not just cancer cells but also healthy cells in the bone marrow and gastrointestinal system, causing grievous side effects like nausea and anemia.
Smart bomb against cancer
In May, Slamon reported to the American Society of Clinical Oncology on a randomized test of Herceptin in 469 patients with aggressive, metastatic (spreading) breast cancer. (Since the data have yet to be published in a research journal, The Why Files is relying here on press releases and public pronouncements.) Unfortunately, the doctors who know Herceptin best did not have time to talk with us about the drug.
The response rate for Herceptin plus taxol was 42 percent, far better than the 16 percent for taxol alone.
Herceptin also prevented the disease from getting worse for 7.3 months. Chemotherapy alone started to fail after 4.5 months.
Although Herceptin's side effects were generally much milder than chemotherapy's, some patients did have heart problems which usually responded to drugs or disappeared at the end of Herceptin therapy.
The idea of interfering only with cancer cells rather than all quick-dividing cells is the great promise of fighting cancer with custom-designed molecules. "This drug opens a new frontier in cancer treatment," said Dennis Slamon, director of the Revlon/UCLA Women's Cancer Research Program. Slamon has worked on the HER2 receptor for 12 years. "This proves the paradigm that if we understand what is broken in the malignant cell, we may be able to fix it."
For ethical reasons, new cancer drugs are given to patients who can't benefit much from existing therapy. Generally they're give in combination with the most effective approved drugs. And when Slamon combined Herceptin with the existing anti-cancer drugs Cytoxin and Adriamycin, the response rate was raised by 20 percent compared to Cytoxin and Adriamycin alone. (Tumors "responded" if they shrank in size by at least 50 percent).
The bad news
Although the idea of interfering with errant growth signals does seem elegant, Herceptin did not work for all patients with too many HER2 receptors. Researchers are trying to root out an explanation for this shortcoming.
And despite the improved response to Herceptin, patients are not living much longer. In Slamon's trial, the one-year survival rate was 78 percent for patients getting Herceptin plus chemotherapy, compared to 67 percent for patients getting chemotherapy alone.
A press release from Genentech, the drug's maker, said, "With the data collected to date, there is not any difference in median survival." It's possible that longer follow-ups will show an improvement, but the data do indicate that cancer is mutating to defeat Herceptin, just as it has with most other agents used in the war on cancer.
Still, patients with metastatic breast cancer have few good treatment options, and any advance is welcome against a disease that will kill 43,900 American women in 1998.
And the Herceptin story may extend beyond breast cancer, since some other cancers also have too much HER2. Clinical tests with Herceptin are either under way or planned for ovarian, gastric, endometrial, salivary gland, non-small cell lung, pancreatic, prostate and colorectal cancers. And with several other HER2 blockers also under development, the full story of this designer drug remains to be written.
Herceptin may be promising, but it's not a cure-all. For one thing, it is only suitable for the 25 to 30 percent of breast cancer patients whose tumors have an excess of HER2. (Patients are tested before treatment to select this group.)
-- David Tenenbaum
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