Ribociclib is a novel kinase inhibitor recently added to the Pharmaceutical Benefits Scheme (PBS). It is indicated for the treatment of locally advanced or metastatic breast cancer that is hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative.
Ribociclib selectively inhibits cyclin-dependent kinases (CDK) 4 and 6, enzymes that are important regulators of cell proliferation. Dysregulation of CDK-dependent pathways occurs in many types of cancer and may contribute to uncontrolled cellular growth. In breast cancer cell lines, ribociclib has demonstrated the ability to induce cell-cycle arrest and reduce cell proliferation.
The MONALEESA-2 trial evaluated the safety and efficacy of ribociclib in postmenopausal women with advanced breast cancer. Patients were randomly assigned to receive ribociclib plus letrozole or letrozole plus placebo. The progression-free survival rate was 63% in the ribociclib group compared to 42% in the placebo group at 18 months. Discontinuation due to adverse events occurred in 7.5% of the test group compared to 2.1% of the placebo group. Grade 3 and 4 adverse reactions occurring more frequently in the ribociclib group included neutropenia, leukopenia, abnormal liver function tests, and vomiting. Although patients with a history of cardiac disease or dysfunction were excluded from this study, ribociclib has been associated with prolongation of the QT interval. It should, therefore, be avoided in patients who have or are at significant risk of developing QTc prolongation.
While data from the ongoing MONALEESA-7 trial suggests that ribociclib has clinical benefit in premenopausal women, ribociclib is currently only approved in Australia for use in men and postmenopausal women. To qualify for PBS authority, treatment must also be in combination with anastrozole or letrozole.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016; 375: 1738-48.
- Kisqali® (ribociclib succinate) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals. Approved February 2018.