Wrong Timing of Herceptin Affects The Heart
Herceptin (trastuzumab) can be a powerful cancer suppressor for certain women, although its cardiovascular side effects are known. Now, Canadian research suggests that giving the drug concurrently with chemotherapy carries less cardiac risk than giving it after the chemo.
The study, which is published in the July 5 issue of the New England Journal of Medicine, underlines the fact that patients "need to have proper cardiac monitoring" while on Herceptin, said one outside expert, Dr. Edith Perez, professor of medicine at the Mayo Clinic in Jacksonville, Fla.
The new findings are similar to those found in clinical trials that compared the two treatment approaches, added the study's lead researcher Dr. Heather L. McArthur, now a special fellow at Memorial Sloan-Kettering Cancer Center in New York City. "It's reassuring that the results for concurrent treatment are similar to that found in clinical trials," she said.
McArthur conducted the study while working in Canada with co-author Dr. Stephen Chia, of the British Columbia Cancer Agency, Vancouver.
Herceptin was approved by the U.S. Food and Drug Administration in 1998 for the treatment of women with advanced cancer whose tumors were found to have too much of a protein called HER-2. It is thought that about 20 percent of women with breast cancer have these types of tumors, which are more aggressive than the tumors that do not over-produce HER-2.
McArthur followed 155 women treated for breast cancer in British Columbia between July and December 2005. Of those, 102 received sequential treatment (chemo then Herceptin), and 53 got concurrent treatment. Each group was treated for 52 weeks.
In the sequential treatment group, 22 women (21.6 percent) experienced a cardiac event that required temporary or permanent stopping of their Herceptin. Four women in this group developed suspected or confirmed congestive heart failure -- a side effect associated with Herceptin.
In those who got concurrent treatment, one woman developed a decline in left ventricular ejection fraction, a measurement that reflects how well the heart is pumping blood. She had to stop treatment but then was able to resume. One other woman had congestive heart failure.
The standard of care today is to give Herceptin concurrently with chemo, McArthur noted. In her study, she offered women who had not previously been given Herceptin the drug after they had finished chemotherapy. "Because of the survival benefit, we wanted to make Herceptin available to those who had had chemo in the last 12 months," she explained. The study was also designed to determine if results in everyday clinical practice would be the same as those found in clinical trials.
Perez, who led some of those clinical trials, said the new "community-based" study is "valuable, because it tells the experience of patients [not in a clinical trial]. It's good to have data in the real world, compared to clinical trials."
But she does not believe the numbers in the study were large enough to definitely conclude that sequential therapy leads to more cardiac problems.
Perez said the rates of congestive heart failure found in McArthur's study in the sequential group are slightly higher than those she found in the clinical trial she conducted. "They saw about 4 percent, we saw 2.5 percent, using a pretty similar regimen of chemotherapy," she said.
She said she is preparing to publish more data from her clinical trial, comparing sequential versus concurrent approaches to giving Herceptin. "We showed a three-year cumulative incidence of congestive heart failure of 2.8 percent in the sequential group and 3.3 percent in the concurrent," Perez said. That difference, she said, is not statistically significant.
One of the weaknesses of the McArthur study, Perez said, is that it is not a randomized study. Various studies on Herceptin and its cardiac effects may also be using different definitions of cardiac toxicity, she added.
What are the practical implications of the Canadian research? One thing is certain: "Herceptin saves lives," Perez said. "I would recommend that all women eligible to receive Herceptin get this drug."
But proper cardiac monitoring is also in order for these patients, she added. Every three months during Herceptin use, women should be evaluated for cardiac function, even if they have no symptoms that suggest heart trouble. This monitoring should include evaluation of the left ventricular ejection fraction to monitor the ability of the heart to pump blood, Perez said.