On March 13, 2017, ribociclib (Kisqali; Novartis) became the third CDK4/CDK6 inhibitor to be approved by the FDA. The FDA approved ribociclib, in combination with an aromatase inhibitor, for the treatment of postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer. Ribociclib received a breakthrough therapy designation and was approved under the FDA’s priority review process.
This approval was based on the phase 3 MONALEESA-2 clinical trial that included 668 treatment-naïve postmenopausal women with HR-positive, HER2-negative advanced breast cancer. The patients were randomized to ribociclib plus letrozole or placebo plus letrozole.
Ribociclib plus letrozole reduced mortality risk by 44%. The median progression-free survival (PFS) was not reached in the ribociclib plus letrozole combination (95% CI, 19.3-not reached) and was 14.7 months with letrozole and placebo (P <.0001). The ORR was 52.7% versus 37.1%, respectively. In another analysis with an 11-month follow-up, the PFS was 25.3 months with the addition of ribociclib and 16 months with letrozole alone.
“These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer,” said Gabriel N. Hortobagyi, MD, Professor of Medicine, Department of Breast Medical Oncology, M.D. Anderson Cancer Center, Houston, and principal investigator of MONALEESA-2.
The most common all-grade adverse reactions with ribociclib plus letrozole included neutropenia (75%), leukopenia (33%), headache (22%), back pain (20%), nausea (52%), diarrhea (35%), vomiting (29%), constipation (25%), alopecia (33%), and fatigue (37%). Dose reductions because of adverse reactions were 45% with the active combination versus 3% with letrozole and placebo. Permanent discontinuation of therapy was reported in 7% of patients versus 2%, respectively.