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...

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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. 

Efficacy—KISQALI + AI in Premenopausal

 

KISQALI—it's not just living longer. It's living well.
 

Overall Survival

Nearly 5 years median overall survival for first-line premenopausal patients

MONALEESA-7: KISQALI + AI in 1L premenopausal patients

At a median follow-up of 54 months

KISQALI® (ribociclib) overall survival in premenopausal HR+/HER2- metastatic breast cancer patients: 58.7 months mOS ~1-year increase
Hazard ratios are based on unstratified Cox model.
  • Results from the 54-month analysis were not prespecified and were observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error
 

At a median follow-up of 35 months

Statistical significance was established for overall survival in the first-line (ITT) population; P=0.00973 (HR=0.71 [95% CI: 0.54-0.95]).2

  • In the subgroup of patients who received tamoxifen, an increased risk for QT prolongation was observed. KISQALI is not indicated for concomitant use with tamoxifen3

PFS: In the primary analysis at a median follow-up of 19 months, mPFS was 27.5 months with KISQALI + NSAI + goserelin (95% CI: 19.1-NR) vs 13.8 months with placebo + NSAI + goserelin (95% CI: 12.6-17.4); HR=0.569 (95% CI: 0.436-0.743).3,4

 

 

Watch Dr Sara A. Hurvitz discuss overall survival, time to chemotherapy, and quality-of-life data for KISQALI in premenopausal patients.

Time to Chemotherapy

Median time to chemotherapy delayed over 4 years

At a median follow-up of 54 months

Median time to chemotherapy 50.9 months over 1-year increase with KISQALI + NSAI
  • Time to chemotherapy was an exploratory end point and was defined as the time from randomization to the beginning of the first chemotherapy after discontinuing study treatment2
  • There was no prespecified statistical procedure controlling for type 1 error

 

Quality of Life

Quality of life improved

At a median follow-up of 35 months

34.2 months mTTD with KISQALI + NSAI + goserelin

Quality of life was assessed using the EORTC QLQ-C30 questionnaire—a validated tool used worldwide to assess quality of life in patients with cancer.5

  • Quality of life was a secondary end point measured by patient-reported outcomes and was assessed at baseline and throughout treatment
  • Time to deterioration was defined as a decline of at least 10% of the global health status/QOL scale score
  • There was no prespecified statistical procedure controlling for type 1 error
  • The EORTC QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status/QOL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation, and diarrhea) and perceived financial impact of the disease6
    • EORTC QLQ-C30 was completed at baseline and ≥1 postbaseline time point by 90% and 83% of patients in the KISQALI and placebo arms, respectively5

Study design: MONALEESA-7 was a randomized, double-blind, placebo-controlled phase III study of KISQALI + ET (NSAI or tamoxifen) + goserelin vs placebo + ET (NSAI or tamoxifen) + goserelin (ITT) in premenopausal patients with HR+/HER2- mBC who received no prior ET for advanced disease. KISQALI is not indicated for concomitant use with tamoxifen. Efficacy results are from a prespecified subgroup analysis of 495 patients who received KISQALI (n=248) or placebo (n=247) with an NSAI + goserelin and were not powered to show statistical significance. OS was a secondary end point; PFS was the primary end point.3,4

For information about KISQALI + fulvestrant in postmenopausal patients, continue to the next page >

1L=first line; AI=aromatase inhibitor; EORTC QLQ-C30=European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; ET=endocrine therapy; HR=hazard ratio; ITT=intent to treat; mBC=metastatic breast cancer; mOS=median overall survival; mPFS=median progression-free survival; mTTC=median time to chemotherapy; mTTD=median time to deterioration; NR=not reached; NSAI=nonsteroidal aromatase inhibitor; OS=overall survival; PFS=progression-free survival; QOL=quality of life.

References: 1. Data on file. Novartis Pharmaceuticals Corp; 2020. 2. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/NEJMoa1903765 3. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022. 4. Tripathy D, Im S-A, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915. 5. Harbeck N, Franke F, Villanueva-Vazquez R, et al. Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7). Ther Adv Med Oncol. 2020;12:1758835920943065. doi:10.1177/1758835920943065 6. Fayers PM, Aaronson NK, Bjordal K, et al. EORTC QLQ-C30 Scoring Manual (3rd edition). 2001.

 

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”), 1.1% of KISQALI-treated patients had ILD/pneumonitis of any grade, 0.3% had grade 3 or 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) have been reported in patients treated with KISQALI in the postmarketing setting.

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 SCARs 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, 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 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.