The international, randomised phase 3 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. Prof. Sara Hurvitz (UCLA Jonsson Comprehensive Cancer Center, USA) noted that for the first time, a statistically significant improvement in overall survival has been observed with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR+/HER2–advanced breast cancer .
Ribociclib is a therapy that inhibits the activity of cancer cell-promoting enzymes known as cyclin-dependent 4/6 kinases (CDK 4/6). 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 oral ribociclib 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 or anastrozole, 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.
In total, 672 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 ribociclib, 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.
“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 Prof. Hurvitz. “The use of ribociclib as a front-line therapy significantly prolonged overall survival, which is good news for women with this terrible disease.”
- Hurvitz S et al. Abstract LBA1008. Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: overall survival (OS) results. ASCO 2019, 31 May-4 June, Chicago, USA.