The US Food and Drug Administration (FDA) today approved ribociclib (Kisqali, Novartis) in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

Ribociclib's approval is based on interim analysis results from the pivotal phase 3 MONALEESA-2 trial involving 668 postmenopausal women who received no prior systemic therapy for their advanced breast cancer.

The trial demonstrated that ribociclib plus the aromatase inhibitor letrozole reduced the risk for progression or death by 44% over letrozole alone (median progression-free survival [PFS] not reached [95% confidence interval (CI), 19.3 months - not reached] vs 14.7 months [95% CI, 13.0 - 16.5 months]; hazard ratio, 0.556 [95% CI, 0.429 - 0.720]; P < .0001).

The results were presented at the 2016 European Society for Medical Oncology Congress and simultaneously published in the New England Journal of Medicine.

Since these data were published, a subsequent analysis with an additional 11 months of follow-up showed that the median PFS was 25.3 months with the ribociclib combination vs 16 months with letrozole alone, according to a company statement.

Ribociclib is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. CDK4/6 inhibition has been shown to overcome or delay resistance to endocrine therapy and has become an established treatment strategy since the first drug in the class, palbociclib (Ibrance, Pfizer), was approved by the FDA last year, as reported by Medscape Medical News.

"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, from the University of Texas MD Anderson Cancer Center in Houston and a MONALEESA-2 principal investigator, in the statement.

The most common adverse reactions (incidence ≥ 20%) are neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain, according to the FDA prescribing information.

The most common grade 3/4 adverse events reported by at least 5% of the ribociclib combination and letrozole alone patients, respectively, were neutropenia (59% vs 1%), leukopenia (21% vs 1%), hypertension (10% vs 11%), and elevated alanine aminotransferase (9% vs 1%). Discontinuation rates because of adverse events were 7.5% and 2.1%, respectively.

The new drug is accompanied by warnings and precautions about QT interval prolongation and hepatobiliary toxicity. With regard to the former, clinicians are advised to monitor electrocardiograms and electrolytes prior to initiation of treatment. With regard to the latter, increases in serum transaminase levels have been observed. Clinicians are advised to perform liver function tests (LFTs) before initiating treatment. Monitor LFTs every 2 weeks for the first two cycles, at the beginning of each subsequent four cycles, and as clinically indicated.

Ribociclib is taken with or without food as a once-daily oral dose of 600 mg (three 200-mg tablets) for 3 weeks, followed by 1 week off treatment. Ribociclib is taken in combination with 4 weeks of any aromatase inhibitor including letrozole.

Ribociclib was reviewed and approved under the FDA Breakthrough Therapy designation and Priority Review programs.

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