Ribociclib (Kisqali®) is a CDK 4/6 inhibitor first approved by the U.S. Food and Drug Administration (FDA) in early 2017 for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine therapy, based on the MONALEESA trial results (see sidebar).
In 2018, the FDA expanded the indication to also include pre- and perimenopausal women and added an indication for use in combination with fulvestrant for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer as initial endocrine-based therapy or following disease progression on endocrine therapy. Ribociclib is currently in active clinical trials for other tumor types such as liposarcoma, meningioma, endometrial, ovarian, and glioblastoma.
Targeted therapy/kinase inhibitor
In combination with an aromatase inhibitor, ribociclib is indicated for the treatment of pre- or perimenopausal or postmenopausal women with HR-positive, HER2-negative, advanced or metastatic breast cancer, as initial endocrine-based therapy. In combination with fulvestrant, ribociclib is indicated for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer as initial endocrine-based therapy or following disease progression on endocrine therapy.
Starting dose is 600 mg orally (three 200 mg tablets) taken once daily for 21 consecutive days followed by 7 days off treatment.
Ribociclib is taken orally, with or without food.
Neutropenia (75% [58% grade 3 or 4]), nausea (52%), hepatobiliary toxicity (18% [8% grade 3]), fatigue (37%), diarrhea (35%), leukopenia (33%), alopecia (33%), vomiting (29% [4% grade 3]), constipation (25%), headache (22%), back pain (20%), QTc prolongation (16%)
Because of QTc prolongation, ribociclib cannot be used in combination with tamoxifen. Monitor electrocardiograms and electrolytes prior to initiation of treatment, on day 14 of the first cycle, at the beginning of the second cycle, and as needed. Monitor electrolytes at the beginning of each cycle for six cycles and as needed.
Because of the risk for neutropenia, monitor complete blood counts before initiating therapy, every two weeks for the first two cycles, at the beginning of each subsequent four cycles, and as needed.
Because of hepatobiliary toxicity risk, monitor liver function tests at baseline and every two weeks for the first two cycles, at the beginning of each subsequent four cycles, and as needed.
Because of embryonal toxicity, women of reproductive potential should have a pregnancy test prior to starting treatment and use proper contraception during treatment. Do not breastfeed.
Drug-Drug and Drug-Food Interactions
Avoid concurrent use with strong CYP3A inhibitors, strong CYP3A inducers, and drugs known to prolong QTc interval. Patients should avoid pomegranate or pomegranate juice and grapefruit or grapefruit juice.
Make sure patients understand their disease and treatment plan. Review dosing, administration instructions, monitoring, what adverse reactions to expect, when and who to notify if an adverse reaction occurs, storage, and safe handling.
Ribociclib is considered a hazardous drug because of the reproductive risk.