The international, randomised phase III MONALEESA-7 trial found that adding ribociclib to standard-of-care endocrine therapy significantly improved overall survival for premenopausal women with advanced HR-positive/HER2-negative breast cancer compared with endocrine therapy alone.
After 42 months of follow-up, the survival rate was 70% for women who took the combination therapy compared with 46% for women who received endocrine therapy only.
Advanced breast cancer is the leading cause of cancer death in women 20 to 59 years of age.
The study was featured in a press briefing and presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
“This is the first study to show improved survival for any targeted therapy when used with endocrine therapy as a first- line treatment for advanced breast cancer,” said lead study author Sara A. Hurvitz, MD, Director of the Breast Cancer Clinical Research Program at UCLA Jonsson Comprehensive Cancer Center in Los Angeles, CA.
“The use of ribociclib as a front-line therapy significantly prolonged overall survival, which is good news for women with this terrible disease.”
Advanced breast cancer is less common in premenopausal women than in older women, and incidence is increasing. In the United States, in women ages 20 to 39, the incidence of advanced breast cancer increased 2% per year between 1978 and 2008.
Ribociclib is a therapy that inhibits the activity of cancer-cell promoting enzymes known as cyclin-dependent 4/6 kinases (CDK 4/6).
In July 2018, the U.S. Food and Drug Administration approved the expanded indication for ribociclib in combination with an aromatase inhibitor to include pre- and perimenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer.
MONALEESA-7 is the first trial to focus exclusively on women under age 59 who were premenopausal and had advanced breast cancer for which they had not received prior endocrine therapy.
Investigators randomly assigned women to ribociclib (a tablet), or to a placebo tablet.
All women also received goserelin, an injectable endocrine therapy that suppresses oestrogen, and one of three other therapies: the nonsteroidal aromatase inhibitors letrozole (Femara) or anastrozole (Arimidex), which lower oestrogen production, or tamoxifen, which has been used to treat breast cancer for over 40 years and blocks the effects of oestrogen in breast tissue.
Six hundred and seventy-two women were enrolled in the study.
After a median follow-up of 34.6 months, 173 (26%) were still receiving the therapies, with 116 (35%) of the women still receiving ribociclib and 57 (17%) still receiving the placebo.
The women who received ribociclib lived a median of 23.8 months without the disease progressing compared with 13 months for women who received the placebo.
The researchers observed that after 42 months of follow-up, for patients receiving ribocilcib, the survival rate was 70% when given with endocrine therapy compared with 46% when given with placebo.
Overall this represented a 29% relative reduction in the risk of death.
In addition, the survival rate of 71% and 70% for women who took ribociclib in combination with tamoxifen or a nonsteroidal aromatase inhibitor, respectively, compared with a survival rate of 55% and 43%, respectively, for women who received placebo in combination with tamoxifen or aromatase inhibitors only.
The researchers are doing analyses of patient-reported outcomes as well as sub-analyses of the clinical findings, including looking at biomarkers and circulating tumour DNA that may help them determine which women might benefit most from ribociclib.
The investigators are studying the use of ribociclib in women and men with early-stage HR , HER2-negative breast cancer in combination with endocrine therapy and other cancer indications.