Featured Research

from universities, journals, and other organizations

Combination of everolimus and exemestane improves survival for women with metastatic breast cancer, results show

Date:
December 8, 2011
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
In an international Phase III randomized study, everolimus, when combined with the hormonal therapy exemestane, has been shown to dramatically improve progression-free survival, according to research.

In an international Phase III randomized study, everolimus, when combined with the hormonal therapy exemestane, has been shown to dramatically improve progression-free survival, according to research from The University of Texas MD Anderson Cancer Center.

The study, known as Breast Cancer Trials of Oral Everolimus (BOLERO-2), was presented Dec. 7 at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium by Gabriel Hortobagyi, M.D., professor and chair of MD Anderson's Department of Breast Medical Oncology. Earlier findings were simultaneously reported in the New England Journal of Medicine.

Everolimus, an immunosuppressant agent first used to prevent rejection of organ transplants, also has anti-angiogenic properties. It inhibits the mammalian target of rapamycin (mTOR) protein, a central regulator of tumor cell division and blood vessel growth in cancer cells; the mTOR pathway is activated in hormone-resistant breast cancer, explained Hortobagyi. Currently, the oral agent is approved for both the treatment of kidney cancer and pancreatic neuro-endocrine tumors, with MD Anderson's research leading the way for the latter's usage approval by the FDA.

Preliminary BOLERO-2 data were first presented at ESMO and showed a significant progression-free survival benefit; these updated findings represent six additional months of patient follow-up, Hortobagyi explained.

"This study is based on the concept that we now know more about the resistance mechanisms to endocrine therapy and the experimental arm of BOLERO-2 uses a dual-attack on treatment refractory hormone receptor-positive breast cancer: it simultaneously inhibits the estrogen-signaling pathway with the aromatase inhibitor, exemestane, and the PI3-kinase/AKT/mTOR pathway with the use of everolimus," Hortobagyi said. "For the first time in a large Phase III trial, we have demonstrated that this dual-attack is more effective than a single endocrine treatment for patients who have received prior endocrine therapy."

The international Phase III trial enrolled 724 metastatic breast cancer patients, all of whom were post-menopausal, had hormone receptor-positive disease and evidence of progressive disease. In a two-to-one ratio, 485 women were randomized to receive the combination of everolimus (10 mg daily), and exemestane, an aromatase inhibitor, and compared to 239 women who received exemestane and placebo. All were previously treated with and progressed on letrozole and anastrozole, with the majority of women extensively treated with prior therapies. The median age of the women enrolled was 62 years; the study's primary endpoint was progression-free survival.

In patients receiving the everolimus combination, researchers found a progression-free survival of 7.4 months, compared to 3.2 months in those who took exemestane alone, a finding Hortobagyi describes as "highly significant." The clinical benefit rate -- complete responses, partial responses and stability exceeding six months -- was 50.5 percent in those in the combination arm, compared to 25.5 percent in those who received the hormonal therapy alone. Adverse effects, such as shortness of breath, hyperglycemia, mouth sores and fatigue, were all higher in the combination group, but were manageable and did not disrupt patients' quality of life, the researchers found. Survival data are still being analyzed.

Because aromatase inhibitors are associated with bone loss and fractures, as a safety measure, Hortobagyi and the researchers assessed patients for bone-turnover markers. The addition of everolimus was found to significantly reduce the level of such markers -- an interesting area for future study, noted Hortobagyi.

"Over the years, our treatment approach for such women with metastatic breast cancer has been sequential use of as many hormone therapies as possible, keeping metastatic disease under control for as long as possible. These findings may allow us to change our approach. In this group of heavily pre-treated patients, all of whom progressed on prior endocrine therapy, the addition of this mTOR inhibitor resulted in significant prolongation of progression-free survival and an improved response rate, with only a modest addition of toxicity," said Hortobagyi.

Hortobagyi believes that these findings may be practice-changing for women who meet the criteria for BOLERO-2. Additional studies are planned with everolimus in breast cancer, including in combination with an aromatase inhibitor in the adjuvant setting, as well as additional clinical trials in the metastatic setting.

In addition to Hortobagyi, authors on the international study include: Jorge Baselga, M.D., Massachusetts General Hospital Cancer Center and Harvard Medical School, and the NEJM study's corresponding author; Martine Piccart, M.D., Jules Bordet Institute; Hope S. Rugo, M.D., University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center; Howard Burris, M.D., Sarah Cannon Research Institute; Mario Campone, M.D., Institut de Cancιrologie de l'Ouest; Shinzaburo Noguchi, M.D., Osaka University; Michael Gnant, M.D., Comprehensive Cancer Center, Medical University of Vienna; Kathleen Pritchard, M.D., Sunnybrook Odette Cancer Centre; Luc Vittori, Zhiying Xu, Ph.D., Pabak Mukhopadhyay, Ph.D., Tarek Sahmoud, M.D., Ph.D. and David Lebwohl, M.D., the last five of Novartis Pharmaceuticals.

The trial was funded, in part, by Novartis. Hortobagyi reports receiving research funds from, as well as having served as a consultant for, Novartis.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Combination of everolimus and exemestane improves survival for women with metastatic breast cancer, results show." ScienceDaily. ScienceDaily, 8 December 2011. <www.sciencedaily.com/releases/2011/12/111207201747.htm>.
University of Texas M. D. Anderson Cancer Center. (2011, December 8). Combination of everolimus and exemestane improves survival for women with metastatic breast cancer, results show. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2011/12/111207201747.htm
University of Texas M. D. Anderson Cancer Center. "Combination of everolimus and exemestane improves survival for women with metastatic breast cancer, results show." ScienceDaily. www.sciencedaily.com/releases/2011/12/111207201747.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) — The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) — Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) — A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) — The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins