NOW FDA
APPROVED
The only CDK4/6
inhibitor approved
based on a first-line,
phase III study that
met its primary
end point early
KISQALI
IS HERE
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Full Prescribing Information

Indication

KISQALI® is a cyclin dependent kinase inhibitor (CDKi) indicated in combination with letrozole for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as initial endocrine-based therapy.

Important Safety Information

Neutropenia. Neutropenia was the most frequently reported adverse drug reaction (74.3%) and a grade 3/4 decrease in neutrophil count (based on laboratory findings) was reported in 59.6% of patients receiving KISQALI® (ribociclib) plus letrozole in the phase 3 clinical study. The median time to grade 2, 3, or 4 neutropenia was 16 days. The median time to resolution of grade ≥3 (to normalization or grade <3) was 15 days in the KISQALI plus letrozole treatment group. Severity of neutropenia is concentration dependent. Febrile neutropenia was reported in 1.5% of patients receiving KISQALI and letrozole. Treatment discontinuation due to neutropenia was low (0.9%). Perform complete blood count (CBC) before initiating therapy with KISQALI. Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and then as clinically indicated.

Based on the severity of the neutropenia, KISQALI may require dose interruption, reduction, or discontinuation.

Hepatobiliary toxicity. In the phase 3 clinical study, increases in transaminases were observed. Grade 3 or 4 increases in alanine aminotransferase (ALT) (10.2% vs 1.2%) and aspartate aminotransferase (AST) (6.9% vs 1.5%) were reported in the KISQALI and placebo arms, respectively. In the phase 3 clinical study and phase 1b study with ribociclib plus letrozole treatment, 83.8% (31/37) of grade 3/4 ALT or AST elevation events occurred within the first 6 months of treatment. The majority of increases in ALT and AST have been reported without concurrent elevations of bilirubin. Among the patients who had grade ≥3 ALT/AST elevation, the median time-to-onset was 57 days for the ribociclib plus letrozole treatment group. The median time to resolution (to normalization or grade <2) was 24 days in the ribociclib plus letrozole treatment group.

Concurrent elevations in ALT or AST greater than 3 times the upper limit of normal and total bilirubin greater than 2 times the upper limit of normal, with normal alkaline phosphatase, in the absence of cholestasis occurred in 4 (1.2%) patients in the phase 3 clinical study and all patients recovered to normal after discontinuation of KISQALI.

Perform liver function tests (LFTs) before initiating therapy with KISQALI. Monitor LFTs every 2 weeks for first 2 cycles, at the beginning of each subsequent 4 cycles, then as clinically indicated. Based on the severity of the transaminase elevations, KISQALI may require dose interruption, reduction, or discontinuation. Recommendations for patients who have elevated AST/ALT grade ≥ 3 at baseline have not been established.

QT interval prolongation. In the phase 3 study, 1 patient (0.3%) had >500 msec postbaseline QTcF value (average of triplicate), and 9 patients of 329 patients (2.7%) had a >60 msec increase from baseline in QTcF intervals (average of triplicate). These electrocardiogram (ECG) changes occurred within the first 15 days of treatment and were reversible with appropriate management. There were no reported cases of torsades de pointes.

ECG should be assessed prior to initiation of treatment. Treatment with KISQALI should be initiated only in patients with QTcF values <450 msec. Repeat ECG at approximately Day 14 of the first cycle and the beginning of the second cycle, then as clinically indicated.

Appropriate monitoring of serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be performed prior to the initiation of treatment, at the beginning of the first 6 cycles, then as clinically indicated. Any abnormality should be corrected before start of KISQALI therapy.

Avoid the use of KISQALI in patients who already have or who are at significant risk of developing QTc prolongation, including patients with:

  • long QT syndrome
  • uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias
  • electrolyte abnormalities

Avoid using KISQALI with drugs known to prolong QTc interval and/or strong CYP3A inhibitors as this may lead to prolongation of the QTcF interval. Based on the observed QT prolongation during treatment, KISQALI may require dose interruption, reduction, or discontinuation.

Reproductive toxicity. Based on animal data and the mechanism of action, KISQALI can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, ribociclib caused embryo-fetal toxicities in rats and rabbits at maternal exposures that were below and 1.5 times the human clinical exposure, respectively, based on area under the curve (AUC). Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during therapy with KISQALI and for at least 21 days after the last dose.

Adverse reactions. The most common adverse reactions in the KISQALI plus letrozole arm (all grades, incidence ≥20%) were neutropenia (74%), nausea (52%), fatigue (37%), diarrhea (35%), leukopenia, (33%), alopecia (33%), vomiting (29%), constipation (25%), headache (22%), and back pain (20%). The most common grade 3/4 adverse reactions in the KISQALI plus letrozole arm (incidence >2%) were neutropenia (60%), leukopenia (21%), abnormal liver function tests (10%), lymphopenia (7%), and vomiting (4%).

Laboratory abnormalities. The most common laboratory abnormalities in the KISQALI plus letrozole arm (all grades, incidence ≥20%) were leukocyte count decrease (93%), neutrophil count decrease (93%), hemoglobin decrease (57%), lymphocyte count decrease (51%), ALT increase (46%), AST increase (44%), platelet count decrease (29%), and creatinine increase (20%). The most common grade 3/4 laboratory abnormalities in the KISQALI plus letrozole arm (incidence >2%) were neutrophil count decrease (60%), leukocyte count decrease (34%), lymphocyte count decrease (14%), ALT increase (10%), AST increase (7%), and phosphorous decrease (6%).

Recommended starting dose is 600 mg (3 x 200‑mg tablets).

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