IMPORTANT SAFETY INFORMATION


QT interval prolongation. KISQALI has been shown to prolong the QT interval in a concentration-dependent manner. Based on the observed QT prolongation during treatment, KISQALI may require...

See More

Indications. KISQALI is a kinase inhibitor indicated in combination with: an aromatase inhibitor for the treatment of pre/perimenopausal or 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; or fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy

Dosing & Administration

The only once-daily CDK4/6 inhibitor with no meal requirements  The only once-daily CDK4/6 inhibitor with no meal requirements

Convenient Dosing

Treatment partner flexibility—KISQALI can be prescribed in combination with an AI or fulvestrant in HR+/HER2– mBC1

MONALEESA-3 postmenopausal 1L/2L with fulvestrant MONALEESA-3 postmenopausal 1L/2L with fulvestrant

KISQALI IN COMBINATION WITH FULVESTRANT FOR POSTMENOPAUSAL WOMEN1
Dosing for KISQALI in combinations with FULVESTRANT for postmenopausal women
  • When given with KISQALI® (ribociclib), the recommended dose of fulvestrant is 500 mg, administered on Days 1, 15, 29, and once monthly thereafter. Please refer to the full Prescribing Information for fulvestrant1

 

MONALEESA-7 premenopausal 1L with an NSAI and MONALEESA-2 postmenopausal 1L with an AI. MONALEESA-7 premenopausal 1L with an NSAI and MONALEESA-2 postmenopausal 1L with an AI.

KISQALI IN COMBINATION WITH AN AI, REGARDLESS OF MENOPAUSAL STATUS1,2
Dosing for KISQALI in combination with an AI, regardless of menopausal status
  • Please refer to the full Prescribing Information for the recommended dose of the chosen AI
  • In premenopausal women
    • An LHRH agonist should be administered according to current clinical practice guidelines when given with KISQALI and an AI
    • KISQALI, an AI, and an LHRH agonist can all be started on Day 1 with no need to delay treatment1,2

 

The only CDK4/6 inhibitor to offer adjustable dosing with no need for a new prescription or co-pay* mid-cycle1

CONVENIENT DOSE ADJUSTMENTS WITH KISQALI1
Dose adjustments with KISQALI without the need for a new prescription or co-pay

a200-mg tablets.

  • Dose adjustments for ARs should be made in stepwise order by reducing the number of tablets taken1
  • Dose modification of KISQALI is recommended based on individual safety and tolerability1
  • If dose reduction below 200 mg/day is required, discontinue treatment1

AI=aromatase inhibitor; ARs=adverse reactions; CDK=cyclin-dependent kinase.

*May be applicable after appropriate treatment determination.

 

Convenient Packaging Options

For postmenopausal women with HR+/HER2- mBC taking KISQALI in combination with an AI—Convenience all in 1, all at once, with the first and only co-pack in mBC3
Benefits of one 28-day cycle of KISQALI and one 28-DAY cycle of FEMARA co-pack Benefits of one 28-day cycle of KISQALI and one 28-DAY cycle of FEMARA co-pack

KISQALI FEMARA co-pack packaging options KISQALI FEMARA co-pack packaging options
KISQALI FEMARA Co-pack Indication

The KISQALI FEMARA Co-Pack is indicated as initial endocrine-based therapy for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer.

 

Dose Modifications

Clear, straightforward dose adjustments1

Monitoring across all 3 trails and indications Monitoring across all 3 trails and indications

DOSE MODIFICATIONS FOR ADVERSE REACTIONS1,a
Dose modifications for neutropenia Dose modifications for neutropenia

Dose modifications for QT prolongation Dose modifications for QT prolongation

Dose modifications for hepatobiliary toxicity Dose modifications for hepatobiliary toxicity

Dose modifications for other toxicities Dose modifications for other toxicities

ALT=alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common Terminology Criteria for Adverse Events; ECG=electrocardiogram; QTcF=QT interval corrected by Fridericia's formula; TB=total bilirubin; ULN=upper limit of normal.

aGrading criteria from CTCAE v4.03. Adverse reactions not requiring a dose adjustment are not shown. Initiate appropriate medical therapy as clinically indicated.
bGrade 3 neutropenia with single episode of fever >38.3°C or >38°C for more than 1 hour and/or concurrent infection. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
cIncludes clinical symptoms of torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia.

 

For information about mechanism of action, continue to the next page >

 

References: 1. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 2. Tripathy D, Im S, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomized phase 3 trial [published online ahead of print May 24, 2018]. Lancet Oncol. 2018. doi:10.1016/S1470-2045(18)30292-4. 3. Kisqali Femara Co-Pack [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018.

 

Indications
KISQALI is a kinase inhibitor indicated in combination with:
  • an aromatase inhibitor for the treatment of pre/perimenopausal or 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; or
  • fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy

IMPORTANT SAFETY INFORMATION
QT interval prolongation. KISQALI has been shown to prolong the QT interval in a concentration-dependent manner. Based on the observed QT prolongation during treatment, KISQALI may require dose interruption, reduction, or discontinuation. Across clinical trials in patients with advanced or metastatic breast cancer treated with KISQALI in combination with an aromatase inhibitor or fulvestrant (“KISQALI treatment groups”), 14 of 1054 patients (1%) had >500 ms postbaseline QTcF value, and 59 of 1054 (6%) had a >60 ms increase from baseline in QTcF intervals. These ECG changes were reversible with dose interruption and most occurred within the first 4 weeks of treatment. No cases of torsades de pointes were reported. In MONALEESA-2, on the KISQALI + letrozole treatment arm, there was 1 (0.3%) sudden death in a patient with grade 3 hypokalemia and grade 2 QT prolongation. No cases of sudden death were reported in MONALEESA-7 or MONALEESA-3.

Assess ECG prior to initiation of treatment. Initiate treatment with KISQALI only in patients with QTcF values <450 ms. Repeat ECG at approximately Day 14 of the first cycle, at the beginning of the second cycle, and as clinically indicated. Monitor serum electrolytes (including potassium, calcium, phosphorus, and magnesium) prior to the initiation of treatment, at the beginning of each of the first 6 cycles, and as clinically indicated. Correct any abnormality before starting therapy with KISQALI.

Avoid the use of KISQALI in patients who already have or who are at significant risk of developing QT 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 the QT interval and/or strong CYP3A inhibitors, as this may lead to prolongation of the QTcF interval.

Increased QT Prolongation With Concomitant Use of Tamoxifen. KISQALI is not indicated for concomitant use with tamoxifen. In MONALEESA-7, the observed mean QTcF increase from baseline was ≥10 ms higher in the tamoxifen + placebo subgroup compared with the NSAI + placebo subgroup. In the placebo arm, an increase of >60 ms from baseline occurred in 6/90 (7%) of patients receiving tamoxifen, and in no patients receiving an NSAI. An increase of >60 ms from baseline in the QTcF interval was observed in 14/87 (16%) of patients in the KISQALI and tamoxifen combination and in 18/245 (7%) of patients receiving KISQALI plus an NSAI.

Hepatobiliary toxicity. Across clinical trials in patients with advanced or metastatic breast cancer, increases in transaminases were observed. Across all trials, grade 3 or 4 increases in alanine aminotransferase (ALT) (10% vs 2%) and aspartate aminotransferase (AST) (7% vs 2%) were reported in the KISQALI and placebo arms, respectively.

Among the patients who had grade ≥3 ALT/AST elevation, the median time to onset was 85 days and median time to resolution to grade ≤2 was 22 days for the KISQALI treatment groups.

In MONALEESA-2 and MONALEESA-3, concurrent elevations in ALT or AST greater than 3 times the ULN and total bilirubin greater than 2 times the ULN, with normal alkaline phosphatase, in the absence of cholestasis occurred in 6 (1%) patients and all patients recovered after discontinuation of KISQALI. No cases occurred in MONALEESA-7.

Perform liver function tests (LFTs) before initiating therapy with KISQALI. Monitor LFTs every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and 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.

Neutropenia. Across trials, neutropenia was the most frequently reported adverse reaction (AR) (74%), and a grade 3/4 decrease in neutrophil count (based on laboratory findings) was reported in 58% of patients in the KISQALI treatment groups. Among the patients who had grade 2, 3, or 4 neutropenia, the median time to grade ≥2 was 16 days. The median time to resolution of grade ≥3 (to normalization or grade <3) was 12 days in the KISQALI treatment groups. Febrile neutropenia was reported in 1% of patients in the KISQALI treatment groups. Treatment discontinuation due to neutropenia was 0.8%.

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 of the subsequent 4 cycles, and as clinically indicated. Based on the severity of the neutropenia, KISQALI may require dose interruption, reduction, or discontinuation.

Embryofetal toxicity. Based on findings from animal studies and the mechanism of action, KISQALI can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of KISQALI to pregnant rats and rabbits during organogenesis caused embryofetal toxicities at maternal exposures that were 0.6 and 1.5 times the human clinical exposure, respectively, based on area under the curve. 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 3 weeks after the last dose.

Adverse reactions. Across clinical trials of patients with advanced or metastatic breast cancer, the most common ARs reported in the KISQALI treatment groups (pooled incidence ≥20%) were neutropenia (74% vs 5%), nausea (45% vs 27%), infections (41% vs 30%), fatigue (33% vs 30%), diarrhea (30% vs 22%), leukopenia (30% vs 3%), vomiting (27% vs 16%), alopecia (24% vs 12%), headache (24% vs 22%), constipation (24% vs 16%), rash (21% vs 9%), and cough (21% vs 16%). The most common grade 3/4 ARs (reported at a pooled frequency >5%) were neutropenia (59% vs 1%), leukopenia (16% vs 3%), abnormal LFTs (9% vs 2%), and lymphopenia (5% vs 1%).

Laboratory abnormalities. Across clinical trials of patients with advanced or metastatic breast cancer, the most common laboratory abnormalities reported in the KISQALI-containing arm vs placebo arm (all grades, pooled incidence ≥20% and ≥5% higher than placebo arm) were leukocyte count decrease (94% vs 30%), neutrophil count decrease (93% vs 25%), hemoglobin decrease (66% vs 38%), lymphocyte count decrease (61% vs 26%), AST increase (47% vs 38%), ALT increase (44% vs 36%), creatinine increase (38% vs 13%), and platelet count decrease (31% vs 9%). The most common grade 3/4 laboratory abnormalities (incidence >5%) were neutrophil count decrease (59% vs 2%), leukocyte count decrease (32% vs 1%), lymphocyte count decrease (15% vs 4%), ALT increase (10% vs 2%), and AST increase (7% vs 2%).

Please see full Prescribing Information.