Kisqali® Receives FDA Approval as First Line Treatment for HR+/HER2- Metastatic Breast Cancer
by C.H. Weaver M.D.
The US Food and Drug Administration (FDA) has approved the investigational drug Kisqali® (ribociclib, LEE011) for first line treatment of hormone receptor + HER 2- metastatic breast cancer because when combined with Femera (letrozole) the combination benefits all such women and leads to improved survival without cancer recurrence.
The interim results from a large clinical trial were previously presented at the 2016 European Society for Medical Oncology (ESMO) meeting and published in the New England Journal of Medicine demonstrating that the addition of Kisqali®to Femara improved survival without cancer progression by 44%.
Advanced or metastatic breast cancer refers to cancer that originated in the breast, but has spread to several and/or distant sites in the body. The goals of treatment for metastatic breast cancer are to improve duration of survival while maintaining quality of life.
The majority of breast cancers are referred to as HR+, meaning their cancer is stimulated to grow from exposure to the female hormones estrogen and/or progesterone. These patients are treated with endocrine therapy (sometimes referred to as hormone, or anti-estrogen therapy), which reduces the cancer cells’ exposure to estrogen through varying mechanisms. Endocrine therapy has proven extremely effective in reducing HR-positive cancer growth and spread for extended periods of time.
Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that help 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.
The MONALEESA-2 clinical trial directly compared Kisqali plus Femara to Femara alone as initial treatment of 668 postmenopausal women with HR+, human epidermal growth factor receptor 2 negative advanced breast cancer.
Among patients with measurable disease the overall response rate was 52.7% with Kisqali and Femara compared to only 37.1% with Femara alone. After a median follow-up of 15.3 months, Kisqali was also associated with a significant improvement in time to cancer progression.
Breast cancer experts at the meeting believe that CDK4/6 inhibition with Kisqali and other cyclin-dependent kinase inhibitors will be a game changer in the treatment of advanced breast cancer. The key question is whether doctors should use them in all patients or whether some biomarker could be identified to use them more selectively. Doctors do not know whether 100% of patients will benefit, or less.
Reference: Hortobagyi B, Stemmer S, Burris H, et al. First-line Kisqali + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC). Proceedings from the annual meeting of the 2016 European Society for Medical Oncology (ESOM). Abstract LBA1_PR. Presented October 8, 2016.