The Food and Drug Administration has approved ribociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, 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.

Overall survival data is immature but approval was based on improvement in progression-free survival (PFS) among 334 women randomized to receive ribociclib plus letrozole compared to 334 women randomized to receive placebo plus letrozole in phase III MONALEESA-2 (hazard ratio, 0.556; 95% CI: 0.429, 0.720; P less than .0001).

The estimated median PFS had not been reached in the ribociclib-containing arm and was 14.7 months in the placebo-containing arm. Objective response rate in patients with measurable disease was 52.7% (95% CI: 46.6, 58.9) in the ribociclib plus letrozole arm and 37.1% (95% CI: 31.1, 43.2) in the placebo plus letrozole arm, the FDA said in a written statement .

Ribociclib 600 mg or placebo was administered orally once daily for 21 consecutive days, followed by 7 days off, with letrozole 2.5 mg administered orally once daily for 28 days. All patients were postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who received no prior therapy for advanced disease. Treatment continued until disease progression or unacceptable toxicity,

The most common adverse reactions in patients taking ribociclib were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 adverse reactions were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner, the FDA warns.

Ribociclib is the second CDK4/6 inhibitor to receive approval for advanced breast cancer, following the accelerated approval of palbociclib (Ibrance) plus letrozole (Femara) as a first-line treatment for postmenopausal women with ER-postive, HER2-negative metastatic breast cancer in 2015. The FDA expanded the indication for fulvestrant to include use in combination with palbociclib in 2016.

Phase II trial data indicating activity of a third CDK 4/6 inhibitor, abemaciclib, in this patient population was presented at the 2016 ASCO Annual Meeting.

The recommended starting dose of ribociclib is 600 mg orally (three 200-mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment.

Full prescribing information for ribociclib is available here .

Ribociclib is being marketed as Kisqali by Novartis Pharmaceuticals Corp.

On Twitter @NikolaidesLaura