Interstitial lung disease/pneumonitis. Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with KISQALI and other CDK4/6 inhibitors...
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Dosing & Administration
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FLEXIBLE DOSING WITH EITHER AN AI OR FULVESTRANT1 |
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(28-day cycle) |
KISQALI |
AI |
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Week 1 |
✓ |
✓ |
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Week 2 |
✓ |
✓ |
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Week 3 |
✓ |
✓ |
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Week 4 |
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✓ |
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Subsequent Cycles |
Repeat 28-day cycle |
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or |
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(28-day cycle) |
KISQALI |
Fulvestrant |
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Week 1 |
✓ |
✓ |
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Week 2 |
✓ |
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Week 3 |
✓ |
✓ |
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Week 4 |
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Subsequent Cycles |
Repeat 28-day cycle |
Once monthly |
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KISQALI + fulvestrant
(28-day cycle)
WEEK 1
WEEK 2
WEEK 3
WEEK 4
SUBSEQUENT
CYCLES
CYCLES
KISQALI
600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off)
600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off)
Fulvestrant
500 mg
500 mg
✓
✓
Day 1 injection
✓
✓
✓
Day 15 injection (Cycle 1 only)
Repeat 28-day cycle
Once monthly
- When given with KISQALI, the recommended dose of fulvestrant is 500 mg, administered intramuscularly on Days 1, 15, 29, and once monthly thereafter. In male patients, an LHRH agonist should be administered according to current clinical practice guidelines. Please refer to the full Prescribing Information for fulvestrant
- In premenopausal patients, an LHRH agonist should be administered according to current clinical practice guidelines when given with KISQALI and an AI
KISQALI + AI
(28-day cycle)
WEEK 1
WEEK 2
WEEK 3
WEEK 4
KISQALI
600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off)
600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off)
AI
Once daily throughout the 28-day cycle, may be taken at the same time as KISQALI
Once daily throughout the 28-day cycle, may be taken at the same time as KISQALI
✓
✓
✓
✓
✓
✓
✓
- Please refer to the full Prescribing Information for the recommended dose of the chosen AI
- In premenopausal patients, an LHRH agonist should be administered according to current clinical practice guidelines when given with KISQALI and an AI
Dr Nick McAndrew shares his perspectives on simple dose reductions with KISQALI and how to improve adherence in patients with HR+/HER2- mBC.
Dose Adjustments
THE ONLY CDK4/6 INHIBITOR THAT OFFERS ONE TABLET STRENGTH FOR SIMPLE DOSE REDUCTIONS
DOSE REDUCTIONS WITH NO NEED FOR A NEW PRESCRIPTION OR ADDITIONAL COST TO PATIENT MID-CYCLE1
- KISQALI is given as 600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off) with either:
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An AI once daily (continuously)
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In premenopausal patients, or men, an LHRH agonist should be administered according to current clinical practice guidelines
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Fulvestrant 500 mg intramuscularly on Days 1, 15, and 29, and once monthly thereafter for postmenopausal patients or men
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In male patients, an LHRH agonist should be administered according to current clinical practice guidelines
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-
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Dose adjustments for adverse reactions should be made in a stepwise order by reducing the number of tablets taken
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Dose modification of KISQALI is recommended based on individual safety and tolerability
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If dose reduction below 200 mg/day is required, discontinue treatment
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KISQALI can be taken with or without food
Straightforward dose adjustments1
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INTERSTITIAL LUNG DISEASE/PNEUMONITIS |
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Grade 1 |
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Grade 2 |
Dose interruption until recovery to grade ≤1, then consider resuming KISQALI at the next lower dose level
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Grade 3 |
Discontinue KISQALI |
- For grade 2 ILD/pneumonitis, an individualized benefit-risk assessment should be performed when considering resuming KISQALI
Interstitial lung disease/pneumonitis
Grade 1 (asymptomatic)
- No dose interruption or adjustment is required
- Initiate appropriate medical therapy and monitor as clinically indicated
Grade 2 (symptomatic)
Dose interruption until recovery to grade ≤1, then consider resuming KISQALI at the next lower dose level
- If grade 2 recurs, discontinue KISQALI
Grade 3 (severe symptomatic) or Grade 4
Discontinue KISQALI
- For grade 2 ILD/pneumonitis, an individualized benefit-risk assessment should be performed when considering resuming KISQALI
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CUTANEOUS ADVERSE REACTIONS, INCLUDING SCARs |
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Grade 1 or Grade 2 |
No dose adjustment is required
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Grade 3 |
Interrupt KISQALI until the etiology of the reaction has been determined. If etiology is not a SCAR
If etiology is a SCAR, permanently discontinue KISQALI |
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Grade 4 |
Permanently discontinue KISQALI |
- SJS (grade 3 and 4) is skin sloughing covering <10% BSA and 10%-30% BSA, respectively, with associated signs. TEN (grade 4) is defined as skin sloughing covering ≥30% BSA with associated symptoms
- Signs and symptoms of SJS and TEN include erythema, purpura, epidermal detachment, and mucous membrane detachment
Cutaneous adverse reactions, including SCARs
Grade 1 or Grade 2
(<10% and 10%-30% of BSA, respectively, with active skin toxicity, no signs of systemic involvement)
(<10% and 10%-30% of BSA, respectively, with active skin toxicity, no signs of systemic involvement)
No dose adjustment is required
- Initiate appropriate medical therapy and monitor as clinically indicated
Grade 3
(severe rash not responsive to medical management; >30% BSA with active skin toxicity, signs of systemic involvement present; SJS)
(severe rash not responsive to medical management; >30% BSA with active skin toxicity, signs of systemic involvement present; SJS)
Interrupt KISQALI until the etiology of the reaction has been determined. If etiology is not a SCAR
- Interrupt dose until recovery to grade ≤1; resume at same dose level
- If reaction still recurs at grade 3, resume at next lower dose level
If etiology is a SCAR, permanently discontinue KISQALI
Grade 4
(any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences; TEN)
(any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences; TEN)
Permanently discontinue KISQALI
- SJS (grade 3 and 4) is skin sloughing covering <10% BSA and 10%-30% BSA, respectively, with associated signs. TEN (grade 4) is defined as skin sloughing covering ≥30% BSA with associated symptoms
- Signs and symptoms of SJS and TEN include erythema, purpura, epidermal detachment, and mucous membrane detachment
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NEUTROPENIA |
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Grade 1 or Grade 2 |
No dose adjustment required |
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Grade 3 (afebrile) |
Interrupt dose until recovery to grade ≤2; resume at the same dose
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Grade 3 (febrile) |
Interrupt dose until recovery to grade ≤2; resume at next lower dose |
- Grade 3 febrile neutropenia with single episode of fever >38.3°C or >38°C for more than 1 hour and/or concurrent infection
Neutropenia
Grade 1 or Grade 2
(ANC 1000/mm3 - < LLN)
(ANC 1000/mm3 - < LLN)
No dose adjustment required
Grade 3 (afebrile)
(ANC 500/mm3 - <1000/mm3)
(ANC 500/mm3 - <1000/mm3)
Interrupt dose until recovery to grade ≤2
- Resume at same dose
- If grade 3 recurs, interrupt dose until recovery; resume at next lower dose
Grade 3 (febrile)
or Grade 4 (ANC <500/mm3)
or Grade 4 (ANC <500/mm3)
Interrupt dose until recovery to grade ≤2; resume at next lower dose
- Grade 3 febrile neutropenia with single episode of fever >38.3°C or >38°C for more than 1 hour and/or concurrent infection
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QT PROLONGATION |
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ECGs with QTcF >480 ms |
Interrupt dose until recovery to <481 ms
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ECGs with QTcF >500 ms |
Interrupt dose if QTcF >500 ms; on recovery to <481 ms, resume at next lower dose
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- ECGs should be assessed prior to initiation of treatment. Repeat ECGs at approximately Day 14 of the first cycle and at the beginning of the second cycle, and as clinically indicated. In case of QTcF prolongation at any given time during treatment, more frequent ECG monitoring is recommended
QT prolongation
ECGs with QTcF >480 ms
Interrupt dose until recovery to <481 ms
- If first occurrence, resume at next lower dose
- If QTcF ≥481 ms recurs, interrupt dose until QTcF resolves to <481 ms; then resume at next lower dose
ECGs with QTcF >500 ms
Interrupt dose if QTcF >500 ms; on recovery to <481 ms, resume at next lower dose
- Permanently discontinue if QTcF interval prolongation is either >500 ms or >60 ms change from baseline AND associated with torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia
- ECGs should be assessed prior to initiation of treatment. Repeat ECGs at approximately Day 14 of the first cycle and at the beginning of the second cycle, and as clinically indicated. In case of QTcF prolongation at any given time during treatment, more frequent ECG monitoring is recommended
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ALT AND/OR AST ELEVATION |
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Grade 1 (> ULN - 3 × ULN) |
No dose adjustment required |
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New Grade 2 |
Interrupt dose until recovery to ≤ baseline; resume at same dose
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Grade 3 |
Interrupt dose until recovery to ≤ baseline; resume at next lower dose
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Grade 4 (>20 × ULN) |
Discontinue |
ALT and/or AST elevation without TB increase >2 x ULN
Grade 1 (> ULN - 3 x ULN) or Grade 2 at baseline (>3 - 5 x ULN)
No dose adjustment required
New Grade 2
(>3 - 5 x ULN)
(>3 - 5 x ULN)
Interrupt dose until recovery to ≤ baseline; resume at same dose
- If grade 2 recurs, resume at next lower dose
Grade 3
(>5 - 20 x ULN)
(>5 - 20 x ULN)
Interrupt dose until recovery to ≤ baseline; resume at next lower dose
- If grade 3 recurs, discontinue
Grade 4 (>20 x ULN) or Grade ≥2 with TB >2 x ULN without cholestasis
Discontinue
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OTHER TOXICITIES |
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Grade 1 or Grade 2 |
No dose adjustment required; initiate appropriate medical therapy and monitor as clinically indicated |
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Grade 3 |
Interrupt dose until recovery to grade ≤1; resume at same dose
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Grade 4 |
Discontinue |
- Grading criteria from CTCAE v4.03. Adverse reactions not requiring a dose adjustment are not shown. Initiate appropriate medical therapy as clinically indicated
- Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment
Other toxicities
Grade 1 or Grade 2
No dose adjustment required; initiate appropriate medical therapy and monitor as clinically indicated
Grade 3
Interrupt dose until recovery to grade ≤1; resume at same dose
- If grade 3 recurs, resume at next lower dose
Grade 4
Discontinue
- Grading criteria from CTCAE v4.03. Adverse reactions not requiring a dose adjustment are not shown. Initiate appropriate medical therapy as clinically indicated
- Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment
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SELECT DRUG INTERACTIONS |
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Strong CYP3A4 inhibitors |
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Strong CYP3A4 inducers |
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Sensitive CYP3A substrates |
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Drugs known to prolong QT interval |
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Dose Reduction Data
OVERALL SURVIVAL PRESERVED FOR PATIENTS WHO REQUIRED DOSE REDUCTIONS2
Overall survival benefit proven across pre- and postmenopausal patients who had ≥1 dose reduction
Results are based on a post hoc analysis; efficacy in the placebo comparator arms was not assessed.
The KISQALI FEMARA Co-Pack
The only CDK4/6 inhibitor available in a co-pack3
Available for first-line use in premenopausal and postmenopausal patients3
A convenient prescription process for you and your patients:
- 1 Package
- contains a 28-day supply of both KISQALI and FEMARA
- Separate packages not needed
- 1 Prescription
- for convenient prescription writing
- 1 Co-pay
- covers both KISQALI and FEMARA
Available in all 3 approved KISQALI dose options: KISQALI® (ribociclib) 600 mg (three 200-mg tablets), 400 mg (two 200-mg tablets), and 200 mg (one 200-mg tablet), with FEMARA® (letrozole) 2.5 mg (one 2.5-mg tablet).
When prescribing KISQALI and fulvestrant, 2 prescriptions are needed.
The KISQALI® (ribociclib) FEMARA® (letrozole) Co-Pack is indicated as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
For information about access and resources, continue to the next page >
AI=aromatase inhibitor; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate aminotransferase; BSA=body surface area; CDK=cyclin-dependent kinase; CTCAE=Common Terminology Criteria for Adverse Events; CYP3A=cytochrome P450, family 3, subfamily A; ECG=electrocardiogram; HR=hazard ratio; ILD=interstitial lung disease; IV=intravenously; LHRH=luteinizing hormone-releasing hormone; LLN=lower limit of normal; mBC=metastatic breast cancer; mOS=median overall survival; NR=not reached; NSAI=nonsteroidal aromatase inhibitor; QTcF=QT interval corrected by Fridericia's formula; SCAR=severe cutaneous adverse reaction; SJS=Stevens-Johnson syndrome; TB=total bilirubin; TEN=toxic epidermal necrolysis; ULN=upper limit of normal.
References: 1. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 2. Data on file. Novartis Pharmaceuticals Corp; 2020. 3. Kisqali Femara Co-Pack [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
Indications
KISQALI is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with:
- an aromatase inhibitor as initial endocrine-based therapy; or
- fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women or in men.
IMPORTANT SAFETY INFORMATION
Interstitial lung disease/pneumonitis. Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with KISQALI and other CDK4/6 inhibitors.
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”), 1.6% of patients treated with KISQALI had ILD/pneumonitis of any grade, 0.4% had grade 3/4, and 0.1% had a fatal outcome. Additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported.
Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis, which may include hypoxia, cough, and dyspnea. In patients who have new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis, interrupt treatment with KISQALI immediately and evaluate the patient. Permanently discontinue treatment with KISQALI in patients with recurrent symptomatic or severe ILD/pneumonitis.
Severe cutaneous adverse reactions. Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) can occur in patients treated with KISQALI.
If signs or symptoms of SCARs occur, interrupt KISQALI until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended.
If SJS, TEN, or DiHS/DRESS is confirmed, permanently discontinue KISQALI. Do not reintroduce KISQALI in patients who have experienced SCARs or other life-threatening cutaneous reactions during KISQALI treatment.
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 KISQALI treatment groups, 15 of 1054 patients (1.4%) had >500 ms postbaseline QTcF value, and 61 of 1054 (6%) had a >60 ms increase from baseline in QTcF intervals. These electrocardiogram (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 non-steroidal aromatase inhibitor (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 KISQALI treatment groups, increases in transaminases were observed. Across all trials, grade 3/4 increases in alanine aminotransferase (ALT) (11% vs 2.1%) and aspartate aminotransferase (AST) (8% 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 92 days and median time to resolution to grade ≤2 was 21 days for the KISQALI treatment groups.
In MONALEESA-2 and MONALEESA-3, concurrent elevations in ALT or AST greater than 3 times the upper limit of normal (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 KISQALI treatment groups neutropenia was the most frequently reported adverse reaction (AR) (75%), and a grade 3/4 decrease in neutrophil count (based on laboratory findings) was reported in 62% 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 17 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 1.7% of patients in the KISQALI treatment groups. Treatment discontinuation due to neutropenia was 1%.
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.
Embryo-fetal 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 embryo-fetal 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. Most common (incidence ≥20%) adverse reactions include infections, nausea, fatigue, diarrhea, vomiting, headache, constipation, alopecia, cough, rash, and back pain.
Laboratory abnormalities. Across clinical trials of patients with advanced or metastatic breast cancer, the most common laboratory abnormalities reported in the KISQALI arm (all grades, pooled incidence ≥20%) were leukocytes decreased, neutrophils decreased, hemoglobin decreased, lymphocytes decreased, AST increased, gamma-glutamyl transferase increased, ALT increased, creatinine increased, platelets decreased, and glucose serum decreased.
