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ATLANTA, June 3 — For women with a certain type of breast cancer, the drug Herceptin has represented a major advance, extending lives and preventing tumor recurrence. But for some of those women, the drug never works, and it eventually stops working for others.
Now, an experimental drug promises to help women whose cancer continues to worsen despite taking Herceptin, doctors here said on Saturday.
Some doctors said that the new drug, lapatinib, which the maker GlaxoSmithKline said it would sell under the name Tykerb, would initially be used only as a backup for Herceptin. But after further studies, they said, it may replace Herceptin for some patients, offering a treatment that could be taken as a once-a-day pill rather than as an infusion, which is required for Herceptin.
Results of a clinical trial announced here Saturday at the annual meeting of the American Society of Clinical Oncology showed that Tykerb nearly doubled the time cancer was held in check in women who had stopped taking Herceptin because it was no longer helping.
For the 160 women in the trial who were given both Tykerb and an existing chemotherapy drug called capecitabine, the median time before tumors started growing was about eight and a half months. For the 161 women who got only capecitabine, it was four and a half months. The trial was halted early because it became unethical to continue giving some women only capecitabine, and they were then offered both.
"Those results are quite impressive and clearly more impressive than any of us would have expected," said Dr. Eric Winer, a breast cancer specialist at the Dana-Farber Cancer Institute in Boston, who has been involved in testing the drug.
Dr. Winer, who has consulted for GlaxoSmithKline, predicted at a symposium here that death from the type of breast cancer treated with Herceptin and Tykerb, known as Her-2 positive, would be eliminated within 10 years. In an interview, he conceded that other drugs would have to be developed, but said he was confident they would be.
Still, experts said, Tykerb does not work for all women and has not yet been shown to prolong lives.
GlaxoSmithKline said it planned to apply by the end of the year for approval of Tykerb. If approval is forthcoming, the drug could reach the market in 2007, but the company said it would make it available to appropriate patients before then under rules allowing for compassionate use of unapproved drugs by patients in dire straits.
Both Herceptin, which was approved in 1998 and is sold by Genentech, and Tykerb are aimed at tumors that have an overabundance of a protein called Her-2. Such tumors account for about 20 percent to 25 percent of breast cancer cases.
Both drugs are so-called targeted therapies, in that they hit particular mechanisms used by tumors to grow or survive. In this case the target is Her-2, which juts out of tumor cells and, when activated, sets off a chain reaction inside the cells that spurs the cells to grow and proliferate.
Herceptin binds to the part of Her-2 that juts out, preventing the protein from being activated. Tykerb works inside the cells, stopping the chain reaction from starting. So it may work even if a tumor becomes resistant to Herceptin. Doctors also said they thought the drugs might work well together.
"It shows we're in the next generation of targeted drugs," said Dr. Roy S. Herbst of the M. D. Anderson Cancer Center in Houston. "We're working in patients who have become resistant" to the first generation.
On Friday, an advisory committee to the Food and Drug Administration recommended approval of dasatinib, a drug for certain leukemia patients who are no longer helped by Gleevec, one of the earliest and most successful targeted drugs. Dasatinib will be sold under the name Sprycel by Bristol-Myers Squibb.
One potential advantage of Tykerb over Herceptin is that it may help fight tumors that spread from the breast into the brain.
Such spreading occurs in about 25 percent to 45 percent of women who take Herceptin, Dr. Winer said. Even if a woman's breast tumor is kept in check by Herceptin, tumors in the brain can cause neurological problems like blindness and paralysis and can be fatal.
Herceptin is too big to cross the barrier that protects the brain from most things in the bloodstream. But there is preliminary evidence that Tykerb can enter the brain.
In the clinical trial, cancer spread to the brain in fewer patients getting Tykerb than in those getting only capecitabine, though the results were not statistically significant. Results of another small study released Saturday indicated that Tykerb could somewhat shrink brain tumors that had spread from the breast.
So far, Tykerb has not been shown to cause the heart failure found in a few percent of women who are given Herceptin along with chemotherapy, said Dr. Charles E. Geyer Jr. of Allegheny General Hospital in Pittsburgh, the lead investigator in the trial. However, 4 of the 160 patients who got Tykerb had a small decline in heart function that reversed itself when the drug was stopped, he said.
Dr. Winer of Dana-Farber said he did not think the cardiac safety of Tykerb had been fully established.
Tykerb blocks not only Her-2 but also the epidermal growth factor receptor, another protein that spurs tumor growth. That protein is the target of drugs approved for lung cancer and colon cancer, so Tykerb may have usefulness in other cancers.
Herceptin, which has been used mainly to treat advanced breast cancer, is now increasingly used in early stages of the disease, after tumors have been removed by surgery. Study results announced last year indicated that Herceptin could cut the recurrence of breast cancer by half. Plans are under way to test Tykerb's usefulness in preventing cancer recurrence after surgery.