Index: 2017 FDA Approvals of Oncology Products by Indication

Breast Cancer - Kisqali (ribociclib)

Manufacturer: Novartis Pharmaceuticals Corp

Approval Date: March 13, 2017

FDA approved ribociclib, a CDK4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.

In a randomized, double-blind, placebo-controlled, international clinical trial, postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer who received no prior therapy for advanced disease were randomized to receive letrozole 2.5 mg administered orally once daily for 28 days plus either ribociclib 600 mg or placebo (n = 334) administered orally once daily for 21 consecutive days, followed by 7 days off. A pre-planned interim efficacy analysis demonstrated an improvement in PFS with hazard ratio (HR) of 0.556 (95% CI: 0.429, 0.720; P < .0001). The estimated median PFS had not been reached in the ribociclib-containing arm and was 14.7 months in the placebo-containing arm. ORR 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 most common adverse reactions (ARs)  with ribociclib (> 20%) were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 ARs (reported in > 2%) were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner.