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New Drug Combination Significantly Delays Tumor Progression in Some Forms of Metastatic Breast Cancer

By BCRF | December 5, 2016

Results from the phase III MONALEESA-2 trial confirmed the benefit of adding the CDK4/6 inhibitor ribociclib to standard endocrine therapy in metastatic breast cancer

Anti-estrogen therapies, such as tamoxifen and aromatase inhibitors, are standard therapy for breast cancers that depend on estrogen for growth – known as estrogen receptor-positive (ER+). Despite the success of these therapies, many tumors ultimately become resistant, leading to metastasis (tumor spreading) and death. A new class of drugs, called CDK4/6 inhibitors, has been developed to overcome resistance and work in combination with anti-estrogen therapy.

The MONALEESA-2 trial looked at how well the combination of the new anti-CDK4/6 drug, called ribociclib, and letrozole worked in women with advanced ER+ breast cancer. After 18 months, 63 percent of women treated with both of these drugs had disease that did not get worse. That’s a 44 perfect improvement over women who received only letrozole.

“In my view, this is a practice-changing study,” Dr. Gabriel Hortobagyi, BCRF researcher and lead investigator on the study, told the ASCO Post.

“When ribociclib is approved, this drug will be one of the major choices for advanced breast cancer.”

There are currently two other CDK4/6 inhibitors (palbociclib and abemeciclib) in clinical trials in breast and other cancers. Palbociclib was fast-tracked for FDA approval for treatment of advanced ER+ disease in 2015 based on results from the Phase I/II PALOMA 1 study.  Phase II PALOMA 2 and Phase III PALOMA 3 and now MONALEESA-2 have further confirmed this class of drugs as a viable treatment option in endocrine resistant ER+ metastatic breast cancer.

The ribociclib/letrozole combination treatment in the MONALEESA trial was well tolerated with less than 5 percent of patients reporting adverse events. The most frequently reported side effects in the combination treatment were mainly uncomplicated asymptomatic hematologic effects including myelosuppression, neutropenia, anemia and thrombocytopenia.  Few patients discontinued the trial due to side effects.

To search for ongoing clinical trials with CDK4/6 inhibitors, go to