by Dr. C.H. Weaver M.D. updated 6/2019
Mature results from the Phase III MONALEESA-7 trial evaluating Kisqali® (ribociclib) in combination wiht endocrine-based therapy in premenopausal or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer were published at the American Society of Clinical Oncology annual meeting.
The trial found determined that adding Kisqali to standard endocrine therapy significantly improved overall survival for premenopausal women with advanced HR-positive/HER2-negative breast cancer compared with endocrine therapy alone. This is the first study to show improved survival for combining a precision cancer medicine with endocrine therapy as a first-line treatment for advanced breast cancer.
Kisqali is a selective cyclin-dependent kinase inhibitor-this class of drugs helps slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably. In July 2018, the U.S. Food and Drug Administration approved an expanded indication for Kisqali to be used in combination with an aromatase inhibitor to include pre- and perimenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer.3
MONALEESA-7 is a comparative clinical trial designed to evaluate Kisqali in combination with hormone therapy consisting of tamoxifen or a non-steroidal aromatase inhibitor plus goserelin compared to treatment with tamoxifen or an aromatase inhibitor plus goserelin alone, in premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer in women who had not previously received endocrine therapy for advanced disease.
Kisqali in combination with tamoxifen or an aromatase inhibitor plus goserelin demonstrated an improved time of survival without cancer progression of 23.8 months compared to 13.0 months for tamoxifen or an aromatase inhibitor plus goserelin. Premenopausal women treated with the Kisqali combination therapy saw a response as early as eight weeks. 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.
The Kisqali combination was well tolerated and women taking Kisqali also had a clinically meaningful improvement in pain symptoms as early as eight weeks; this improvement was sustained. The most significant side effect observed in patients receiving Kisqali combination therapy compared to endocrine therapy alone was neutropenia which occurred in 60.6% compared to 3.6% of endocrine only treated patients.
Premenopausal breast cancer is a biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer death in women 20-59 years old.2,3 The Kisqali combination therapy represents a new and improved treatment option for these women.
The drug was approved in the US in March last year for use in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with the disease, an indication for which it was also previously awarded breakthrough status.4
- Tripathy D, Sohn J, Im S, et al. First-line ribociclib or placebo combined with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized Phase III MONALEESA-7 trial. Presented at the San Antonio Breast Cancer Symposium (SABCS), December 6, 2017, San Antonio, Texas (abstract#S2-05).
- Benz CC. Impact of aging on the biology of breast cancer. Crit Rev Oncol Hematol. 2008;66:65-74
- World Health Organization. Women’s health fact sheet. September 2013. Available at http://www.who.int/mediacentre/factsheets/fs334/en/. Accessed October 2017.
- Siegel RL, Miller KD, et al. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians. Vol. 68, No. 1. January/February 2018.
- Johnson RH, Chien FL, et al. Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA. 2013;309:800–5.
- U.S. Food and Drug Administration: FDA expands ribociclib indication in HR-positive, HER2-negative advanced or metastatic breast cancer.
- Tripathy D, Im SA, et al. Lancet Oncol. 2018;19:904-915