Hope for Breast Cancer When Herceptin Fails - Tykerb & Xeloda
An innovative new drug combination may help women with advanced
breast cancer that no longer responds to trastuzumab (Herceptin), researchers report. The investigational drug lapatinib (Tykerb) slows cancer growth by about 50% when given with the drug capecitabine (Xeloda), researchers from Allegheny General Hospital in Pittsburgh announced .
They presented findings from their phase III clinical trial at the annual meeting of the American Society of Clinical Oncology, in Atlanta.
The study involved 321 women with breast cancer that expressed HER2/neu, a protein that makes tumors especially aggressive. About 20%-25% of breast cancers are HER2-positive. The drug Herceptin, which targets HER2, is very effective at treating these advanced cancers, but women eventually develop resistance to it and it stops working.
That was the case with the women in this study. All had tumors that had continued growing or spread, even though they had been treated with chemotherapy and Herceptin.
'Exciting Results'
Lead author Charles Geyer, MD, and his team gave 161 women capecitabine alone, while 160 got capecitabine plus lapatinib. After about a year, researchers saw startling differences between the two groups. On average, it took about 20 weeks for the cancer to start growing again in women who got capecitabine alone. But cancer progression was delayed by about 37 weeks in women who got capecitabine plus lapatinib. That difference was highly statistically significant.
The improvement was so striking that the committee monitoring the study stopped enrollment so that all participants could get the new drug combination.
Side effects were similar in the 2 groups, though women on lapatinib had more cases of diarrhea. Other commonly reported, though mostly mild, side effects were skin rashes and hand-and-foot syndrome, which causes tenderness, redness, drying, and cracking of the soles and palms.
Geyer called these "exciting results" because they offer hope to women with few remaining treatment options.
"Herceptin has completely changed the management of women with HER2 metastatic cancer," he said, "but some patients don't respond to it, and even those who do eventually become resistant."
Such women could eventually benefit from lapatinib, he said.
Same Target, Different Approach
Lapatinib works for women with HER2-positive breast cancer because like Herceptin, it also targets the HER2 receptor. But it does so in a different way, blocking receptors inside the cell. Herceptin blocks receptors on the outside of the cell, Geyer explained.
"It is thought that dual blockage may be better," he said.
The new results show that science is making steady progress toward the goal of individualized treatment for cancer patients, said Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society.
"This increase [in time to progression] of about 17 weeks -- or 4+ months -- is indeed an important element of progress for a group of women where just a couple of years ago the outlook was exceedingly bleak," he noted.
Geyer said future trials will compare Herceptin and lapatinib head-to-head, and should also examine the effects of combining both drugs.
Lapatinib is made by GlaxoSmithKline. It is not yet available in the US because it is not yet approved by the US Food and Drug Administration.
Citation: "A Phase III Randomized, Open-Label, International Study Comparing Lapatinib and Cepecitabine vs. Capecitabine in Women with Resractory Adsvanced or Metastatic Breast Cancer (EGF100151)." Late-breaking abstract presented June 3, 2006, at the ASCO annual meeting. First author: Charles E. Geyer, Jr., MD, Allegheny General Hospital, Pittsburgh
http://www.cancer.org/docroot/NWS/co...ptin_Fails.asp
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