FDA Approves Ribociclib for First-Line Metastatic Breast Cancer

The US Food and Drug Administration (FDA) has approved ribociclib, a CDK4/6 inhibitor, in combination with an aromatase inhibitor for the first-line treatment of postmenopausal women with advanced or metastatic, hormone receptor (HR)-positive/HER2-negative breast cancer.

The approval of ribociclib (Kisqali, Novartis) is based on results from the phase III MONALEESA-2 trial. Results of the trial were presented at the European Society for Medical Oncology (ESMO) 2016 Congress, held in Copenhagen, and published simultaneously in the New England Journal of Medicine.

The trial included 668 postmenopausal women with HR-positive/HER2-negative advanced or metastatic breast cancer; the patients had received no prior therapy. Patients were randomized to either letrozole plus placebo or to letrozole along with ribociclib.

The ribociclib’s median progression-free survival (PFS) was not reached, while the median PFS was 14.7 months with letrozole and placebo, for a hazard ratio of 0.556 (95% CI, 0.429–0.720; P < .0001). In a subsequent analysis with an additional 11 months of follow-up, the median PFS for the ribociclib group was found to be 25.3 months, compared with 16 months without it. Overall survival data remains immature at this point.

“In the MONALEESA-2 trial, ribociclib plus letrozole reduced the risk of disease progression or death by 44% over letrozole alone, and more than half of patients (53%) with measurable disease taking ribociclib plus letrozole experienced a tumor burden reduction of at least 30%,” said Gabriel N. Hortobagyi, MD, of the University of Texas MD Anderson Cancer Center in Houston, in a press release from Novartis. “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-positive advanced breast cancer.”

Ribociclib’s approved dose is 600 mg taken orally once daily for 3 weeks, followed by 1 week off treatment, with 4 weeks of any aromatase inhibitor. In the MONALEESA-2 trial, the most common grade 3 or 4 adverse events included neutropenia in 59.3% of ribociclib patients vs 0.9% of placebo patients, leucopenia (21% vs 0.6%, respectively), hypertension (9.9% vs 10.9%, respectively), among others. Ribociclib was more likely to lead to treatment discontinuation than placebo (7.5% vs 2.1%).