Evista vs. Tamoxifen for Breast Cancer Prevention

Evista (raloxifene) and tamoxifen are both prescribed to treat breast cancer - however, differences in the drugs' safety and tolerability profiles may influence prescribing patterns, according to new research.

For example, Evista may be superior to tamoxifen in a high-risk, post-menopausal woman who has an intact uterus and is not sexually active.

Such perceived trade-offs are the result of the STAR (Study of Tamoxifen and Raloxifene) study, whose results were reported in April and an analysis present at a recent American Society of Clinical Oncology meeting.

Additional reporting on the STAR trial was published in two articles in the Journal of the American Medical Association online on June 5.

Safety and Event Profiles Influence Prescribing

Because Evista is associated with a lower risk of developing uterine cancer, it may be a better drug for treating women with cancer who have a uterus. On the other hand, Evista is associated with a higher risk of vaginal dryness and pain during intercourse, according to Patricia Ganz, MD, of the Jonsson Comprehensive Cancer Center at UCLA, and an author of the STAR quality-of-life analysis.

"I would advise that women should start on one drug and then re-assess in three months," Dr Ganz said, according to MedPage Today. "If the woman had a uterus, I would start her on [Evista], otherwise it would depend upon what is really important to a woman."

The type of adverse events differed between the two drugs. Women taking Evista reported more musculoskeletal symptoms and weight gain, while women taking tamoxifen reported more vaginal discharge, hot flashes, leg cramps and bladder-control symptoms.

However, symptom severity was minor for both tamoxifen and Evista, and tolerance was high in most women, according to Dr Ganz.

STAR Clinical Trial

In the STAR trial, 19,747 high-risk, cancer-free post-menopausal women were randomized to receive either Evista (60 mg) or tamoxifen (20 mg). Participants' average age was 58 years about half were aged 50-59 years. A total of 93.5% of participants were Caucasian, and 70% had at least one first-degree relative with breast cancer.

The study revealed that, after 72 months' follow-up, Evista and tamoxifen were equally effective in preventing invasive breast cancer (the study's primary endpoint). In the tamoxifen group, 163 invasive breast cancers occurred, compared with 168 in the Evista group.

In April, study results strongly suggested that Evista was superior to tamoxifen, because Evista had fewer serious adverse effects (thromboembolic events; cataracts) and a lower risk of hot flashes and night sweats. A lower risk of uterine cancer was also reported (23 vs. 26 cases, respectively).

However, in April, Evista's failure to reduce the risk of non-invasive cancers was downplayed: in fact, fewer cases of non-invasive breast cancer arose in the tamoxifen group (57 cases), compared with the Evista group (80 cases). While this difference did not reach statistical significance, the study may not have been organized so that such a difference would have been detected.

"We have no explanation for this apparent biological difference," said D Lawrence Wickerham, MD, associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the study's senior author. The authors wrote: "the clinical impact of this finding remains to be seen. The mechanism that would allow for a decrease in invasive breast cancers but a lesser impact on noninvasive cancers is unknown."

Dr Wickerham said that Evista and tamoxifen both effectively reduced invasive breast cancer, in all subgroups, "including women with a history of atypical hyperplasia or LCIS [lobular carcinoma in-situ]."

Evista and tamoxifen are also comparable in terms of quality of life, said Dr Ganz. However, unlike tamoxifen, known as a "cancer drug," Evista is currently prescribed by primary-care physicians to hundreds of thousands of women [to prevent osteoporosis], Dr Wickerham reportedly said. This fact makes Evista uniquely appealing as a strategy to prevent breast cancer.

Dr Burstein agreed, saying, according to MedPage Today, "Overall, tamoxifen is the most important drug in the history of oncology. It has saved more lives than any other drug." Compared with placebo for primary prevention of breast cancer, tamoxifen" cut the risk in half in high risk women. But what that meant was that instead of these women having a 5% to 6% risk of breast cancer. They had a 2% to 3% risk - that's a 50% reduction but it doesn't look like much to a healthy women who is being asked to take a drug that causes hot flashes for five years."

Evista has the same benefit, but it is also widely prescribed for preventing osteoporosis.

Cost may not be an issue, although tamoxifen is available in generic form, while Evista is not. Noah D Kauff, MD, of Memorial Sloan-Kettering Cancer Center in New York, noted that the relative costs of Evista and tamoxifen are $75 per month versus $100 per month.

Drug manufacturer Eli Lilly (which markets Evista) reportedly plans to seek FDA approval for labeling that indicates Evista is effective in preventing breast cancer, and Dr Burstein believes that Evista's role in prevention may be significant.

Dr Wickerham confirmed that an Evista-aromatase inhibitor trial is planned. If Evista demonstrates comparable effectiveness in preventing invasive breast cancers, it may prove to be the preferred drug, because it also protects bones. In contrast, drugs such as Arimidex (anastrozole) reduce bone-mineral density.

Finally, in an accompanying editorial, William J Gradishar, MD, and David Cella, PhD, of Northwestern University in Chicago, wrote the "breast cancer chemoprevention sky now includes two shining STARs - tamoxifen and raloxifene. Although neither is a supernova, their benefits include prevention of breast cancer in postmenopausal women at increased risk and, in the case of raloxifene, reduction of fractures related to osteoporosis."

This clinical trial was supported by grants from by AstraZeneca, Eli Lilly and the National Cancer Institute.

Sources: ASCO: Evista or Tamoxifen? The Trade Offs in Preventing Breast Cancer (CME/CE), MedPage Today, June 6, 2006. Effects of Tamoxifen vs. Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes: The NASBP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. Vogel VG, et al, Journal of the American Medical Association, volume 295, June 5, 2006.> Patient-Reported Symptoms and Quality of Life During Treatment with Tamoxifen or Raloxifene for Breast Cancer Prevention The NASBP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. Land SR, et al, Journal of the American Medical Association, volume 295, 2006. Selective Estrogen Receptor Modulators and Prevention of Invasive Breast Cancer. Gradishar WJ and Cella D, Journal of the American Medical Association, volume 295, 2006.

Posted: June 2006


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