The medicine ribociclib (LEE011) may extend progression-free survival when given with the aromatase inhibitor letrozole (Femara) in women with metastatic breast cancer, a phase III trial published in the New England Journal of Medicine found.

Background and Goals

Stage IV, or metastatic, describes a breast cancer that has spread to other organs in the body. People with metastatic breast cancer have to get treatment for the rest of their lives, switching from one medicine or treatment combination to another when a treatment stops having an effect on the cancer.

Cyclin-dependent kinases 4 and 6, CDK 4/6, are two proteins that are too active in many hormone receptor-positive breast cancers, causing tumor cells to multiply. The medicine under study, ribociclib, is a CDK 4/6 inhibitor. It gets in the way of these proteins telling tumor cells to grow.

Previous studies found signs that ribociclib, when given with letrozole, could help keep metastatic breast cancer from growing for longer periods of time than letrozole given alone.

Ribociclib is still being studied and is not available for treatment outside of clinical trials. In September, the U.S. Food and Drug Administration gave ribociclib “breakthrough therapy designation” because research findings show the medicine has great promise in treating metastatic breast cancer. The designation will allow ribociclib to move through the FDA approval process more quickly.

Design

The MONALEESA-2 trial was designed to see if adding ribociclib to the hormonal therapy letrozole would keep the cancer from growing and spreading for a longer period of time than treatment with letrozole given with a placebo. This was a double-blind study, meaning the people getting treatment and the doctors giving the treatment did not know who was getting ribociclib or who was getting the placebo. Everyone in the study was given letrozole. A total of 668 women were included in this analysis and were randomly divided into two groups.

The trial started accepting women who met all of the requirements in December 2013. Participating women had

• metastatic breast cancer
• breast cancer that was hormone receptor-positive and HER2-negative
• gone through menopause
• not previously received treatment for stage IV breast cancer
• never been treated with another CDK4/6 inhibitor

Researchers were interested in progression-free survival, the time from when a person enrolled in the trial to when the cancer showed signs of growing or the person died. Tumors were examined every 2 months for the first year and a half, then every 3 months until the cancer progressed or they reached the end of the study.

The October findings were from the first analysis of this trial, which researchers had decided to perform when at least 211 people had cancers that progressed or had died. Researchers were able to share findings on progression-free survival, but they continue to follow participants for more information on overall survival rates.

Results

Researchers found that people who were receiving ribociclib and letrozole had longer periods of progression-free survival than women who took the placebo and letrozole.

The study found that the rates of people who had not shown progression 18 months after entering the study were

• 63 percent of women taking letrozole with ribociclib
• 42 percent of women taking letrozole with a placebo

Cancers treated with ribociclib responded at a higher rate, according to the researchers. For women with tumors the researchers could measure, they saw 53 percent of tumors shrink in the ribociclib group. That rate for tumors shrinking in women taking the placebo was 37 percent.

Women taking ribociclib did experience side effects more often than the women in the placebo group including neutropenia, nausea and infections. Neutropenia is a decrease in the number of white blood cells that has no physical symptoms. It affected 74 percent of women taking ribociclib. The women in that group also had their dose lowered due to all side effects in 54 percent of cases (7 percent of the placebo group did). Side effects caused 7.5 percent of women to stop taking ribociclib.

What This Means For You

Metastatic breast cancer is a disease you will have to treat for the rest of your life. Getting treatments to work longer means more time when the cancer isn’t growing and more time without having to switch to other medicines and new side effects. Most women in the MONALEESA-2 trial may have experienced side effects, but some showed only in lab tests. Less than 10 percent of women changed to a different treatment because of them.

Ribociclib is a new medicine that is not yet available to the public and this study looked specifically at metastatic breast cancer. As more studies are done with this medicine we will learn more about other cases in which women may be helped by ribociclib and the FDA will consider if it can go to market.

You can enroll in clinical trials to possibly get treatment with the latest medicines and practices and at least the standard of care you would get at your usual cancer center. Speak with your doctor or visit CancerTrials.gov to learn about available trials in your area.

Hortobagyi, G., Stemmer, S., Burris, H., et. al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. New England Journal of Medicine. October 8, 2016. doi: 10.1056/nejmoa1609709