Canadian Cancer Trials Group MAP.3 Results Presented at ASCO
|Final results of Canadian Cancer Trials Group MAP.3 show that exemestane significantly reduces risk of invasive breast cancer in high-risk, postmenopausal women.
These results were chosen to be included in ASCO's Official Press Program and were highlighted during a press conference on Saturday, June 4. MAP.3 was presented by the trial chair, Dr. Paul Goss from Massachusetts General Hospital.
Dr. Goss's presentation received wide media coverage, including in Time Magazine. Here is the link -- http://healthland.time.com/2011/06/06/a-breast-cancer-treatment-works-as-prevention-too/. The Canadian Cancer Society has also highlighted the results of this trial (http://www.cancer.ca/Canada-wide/About%20us/Media%20centre/CW-Media%20releases/CW-2011/CCS%20research%20best%20of%20best%20at%20ASCO.aspx?sc_lang=en), as has the NCI Cancer Bulletin (http://www.cancer.gov/ncicancerbulletin/061411/page4).
Additionally, MAP.3 was published online in the New England Journal of Medicine to coincide with Dr. Goss's presentation. Here is the link to the publication -- http://www.nejm.org/doi/full/10.1056/NEJMoa1103507.
Following is the press release issued by ASCO:
Exemestane Significantly Reduces Risk of Invasive Breast Cancer in High-Risk, Postmenopausal Women
A large randomized double-blind phase III trial led by Canada's Canadian Cancer Trials Group (Canadian Cancer Trials Group) has shown that in postmenopausal women who are at increased risk of developing breast cancer, the aromatase inhibitor (AI) exemestane (Aromasin) reduces this risk by 65 percent compared with placebo.
"The potential public health impact of these findings is important. World-wide it is estimated that 1.3 million women are diagnosed with breast cancer each year and nearly 500,000 women die of the disease. Results from the MAP.3 trial indicate that exemestane is a promising new way to prevent breast cancer in menopausal women most commonly affected with breast cancer," said Paul E. Goss, MD., Ph.D. lead study author and Professor of Medicine at Harvard Medical School and Massachusetts General Hospital, Boston, Mass.
"The reduction in breast cancers of 65% we demonstrated was exactly in line with our expectations," Dr. Goss continued. "The numbers of tumors are small but there also appeared to be fewer of the more aggressive tumors on exemestane. Our study not only showed an impressive reduction in breast cancers, but also an excellent side effect profile, although my cautionary note is that average follow-up to date has been only 3 years."
Estrogens have been implicated in causing breast cancer. The anti-estrogens tamoxifen and raloxifene are FDA approved preventatives of breast cancer in women at high risk. However, it has been estimated that rare but serious uterine cancer and blood clots which can be fatal, have limited the acceptance of tamoxifen to only 4% of high risk women and 0.08% of all women in the U.S. There is a need for highly effective and safer options for breast cancer prevention.
Aromatase inhibitors (AIs) powerfully prevent estrogen synthesis and are distinct from tamoxifen in the way they counteract estrogen. AIs are superior to tamoxifen in preventing recurrences in early breast cancer patients, including the prevention of new breast cancers. The investigators predicted from laboratory experiments and clinical results that AIs would prevent breast cancer without the serious toxicities seen with tamoxifen.
The MAP.3 (Mammary Prevention Trial-.3) study, led and coordinated by the Canadian Cancer Trials Group, is the first randomized trial to assess an aromatase inhibitor as a breast cancer preventative in healthy women. Exemestane is an AI approved by the FDA for use in early breast cancer patients. The trial enrolled 4,560 women from the U.S., Canada, Spain and France. Eligible postmenopausal women had at least one of these risk factors: age ≥60 years; 5-year Gail risk score ≥1.66%; prior atypical d ctal carcinoma in situ with prior mastectomy.
At a median follow up of three years, there were 66 cases of invasive breast cancer and pre-invasive DCIS in women on the trial. The group receiving exemestane had a 65 % reduction in invasive cancers (11 invasive breast cancers in the exemestane group compared to 32in the placebo group), and a 60% reduction in invasive cancers and DCIS lesions combined. Also, there were fewer cases of cancer precursor lesions such as atypical ductal and atypical lobular hyperplasia in the group receiving exemestane.
The investigators reported symptoms such as hot flashes, fatigue sweating, insomnia and arthralgia were frequent in all women on study but predictably slightly more common on exemestane. However these symptoms did not appear to affect self-reports of overall health-related quality of life on exemestane.
More serious adverse events including bone fractures, osteoporosis, hypercholesterolemia, adverse cardiovascular events and other non-breast cancers were equal in both groups.
"After unblinding, women on active therapy will be offered exemestane to complete five years, and MAP.3 sites will have the option of offering 5 years of exemestane to those initially allocated to placebo. We and others are conducting placebo-controlled trials in healthy women and early breast cancer patients of AI's in menopausal women of similar age and results from these ongoing trials will contribute to our understanding of long-term efficacies and toxicities of aromatase inhibitors," Dr. Goss said. "Long-term results in women with early breast cancer show durable long-term reductions in new breast cancers with exemestane without accumulation of late toxicities. So we are hopeful and optimistic that this will be the case in this prevention setting."
The Canadian Cancer Trials Group receives programmatic funding, including for its prevention initiative, from the Canadian Cancer Society Research Institute. Additional support for the Canadian Cancer Trials Group prevention initiative was provided by the Canadian Institutes for Health Research. The MAP.3 trial was supported with funds provided by Pfizer.
As we reported in the previous edition of the Canadian Cancer Trials Group Bulletin, several abstracts related to Canadian Cancer Trials Group trials or trials which included Canadian Cancer Trials Group participation were presented at the American Society of Clinical Oncology Annual Meeting in Chicago, IL, June 3-7, 2011, including Canadian Cancer Trials Group-led MA.20, MAP.3, and PR.7 chosen as among the "Best of ASCO."