CancerConnect News: The CDK4/6 inhibitor Kisqali (ribociclib) has been given breakthrough status by the US Food and Drug Administration as an initial endocrine-based treatment for of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.
Results from the Phase III MONALEESA-7 trial evaluating Kisqali® in combination 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 are the basis for the breakthrough status designation.1
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.
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 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 FDA’s breakthrough designation is designed to speed up development and review of experimental medicines treating serious or life-threatening conditions, when a substantial improvement over an available therapy on at least one clinically significant endpoint has been demonstrated.
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.