SATURDAY, June 3, 2006 (HealthDay News) -- An experimental drug delayed breast cancer progression in women who were no longer responding to Herceptin and facing certain decline, researchers reported Saturday.
When given in combination with chemotherapy, Tykerb (lapatinib) did a better job of curtailing cancer growth than did the chemo drug alone.
"Based on these results, we believe this represents an effective new regimen for women with advanced HER2 breast cancer, and should be considered the new standard of care," said study author Dr. Charles E. Geyer Jr., director of breast medical oncology at Allegheny General Hospital, in Pittsburgh.
Tykerb, which comes in pill form, is made by GlaxoSmithKline, which funded the Phase III trial. The results were announced at a news conference at the American Society of Clinical Oncology (ASCO) annual meeting, in Atlanta.
Announcement of an expanded-access program for the drug while U.S. Food and Drug Administration approval is pending should be made sometime over the weekend or early next week, added Dr. Julie Gralow, a medical oncologist at the University of Washington in Seattle, and moderator of the news conference.
"This is an exciting advance for those with HER2 cancers," she said.
Some 20 percent to 25 percent of breast cancers have abnormally high levels of the HER2/neu receptor and, as a result, are generally more aggressive. Herceptin (trastuzumab) blocks activity of the receptor by binding to the part of the receptor outside the cell. Tykerb, by contrast, binds to a part of the receptor inside the cell.
"Herceptin has completely changed the outlook for women with HER2-positive metastatic breast cancer," Geyer explained, but some patients never respond to the drug and those who do respond become resistant at some point. "Basically, women with metastatic breast cancer eventually derive potential benefit from lapatinib."
Starting in March 2004, 321 women were randomly assigned to receive Tykerb plus Xeloda (capecitabine) or Xeloda alone. All of the participants had metastatic breast cancer that was not responding to taxane, a standard chemotherapy drug, and Herceptin. All participants also had HER2/neu positive breast cancer.
The trial included a plan for an independent data monitoring committee to analyze data at the halfway point to see if the benefits were larger than anticipated, in which case the committee would recommend the study be closed.
On March 20, 2006, the committee made a unanimous recommendation to terminate the trial because the results were so encouraging.
Women in the combined therapy group had almost double the time to disease progression as did women receiving Xeloda alone: 36.9 weeks vs. 19.7 weeks.
"This correlates to a 50 percent reduction in the risk of progressive disease, which met the criteria specified before the trial," Geyer said.
Side effects were roughly the same, but only four women in the Tykerb group experienced brain metastases compared to 11 in the other group. The drug also did not appear to have any negative cardiovascular effects, which was somewhat surprising because experts believe HER2 has a protective effect on the heart muscle. "If that is correct, then one might expect problems with drugs that block HER2," Geyer said.
Three other trials highlighted at the meeting Saturday concerned aromatase inhibitors, a relatively new class of compounds that block estrogen production in the body. Tamoxifen, which has been the gold standard of care in breast cancer treatment for 20 years, hinders the body's ability to use estrogen.
Investigators have shown for the first time that postmenopausal women with early-stage breast cancer who switched to Aromasin (exemestane) after first taking tamoxifen for two to three years had a 15 percent to 17 percent lower risk of dying than those who continued to take tamoxifen for the full five years. Aromasin also reduced the risk of breast cancer recurrence and spread, as well as the development of cancer in the other breast.
A second study found that taking the aromatase inhibitor Arimidex (anastrozole) for five years resulted in a higher degree of bone loss than taking tamoxifen for the same amount of time. Previous research had shown that Arimidex was more effective than tamoxifen in preventing breast cancer recurrence.
Bone health at the beginning of the study seemed to matter, however.
"There wasn't a single patient in this cohort who started with a normal bone-mass density who became osteoporotic over the five-year treatment," said study author Dr. Robert E. Coleman, a professor of medical oncology at Weston Park Hospital in Sheffield, U.K. "The few who did develop low osteoporosis had low bone-mass density to begin with."
Arimidex resulted in a 6 percent to 7 percent loss per year; normal in this age group is 2 percent to 3 percent. To develop osteoporosis, a woman needs to lose 15 percent to 20 percent or more of her normal peak bone mass, Coleman stated.
Finally, a third trial, by Norwegian researchers, found that low levels of vitamin D may actually worsen the bone loss associated with taking Aromasin.
Visit the National Cancer Institute for more on breast cancer.