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 Across 3 Phase III Trials

 

KISQALI—it's not just living longer. It's living well.
Newly diagnosed patients with HR+/HER2- mBC expect a treatment that truly delivers on their goals: Living longer, living well.

NCCN Recommended

National Comprehensive Cancer Network® (NCCN®) now recognizes ribociclib (KISQALI®) + ET, a Category 1 preferred treatment option, for showing an OS BENEFIT IN 1L PATIENTS with HR+/HER2- mBC across endocrine therapy partners and menopausal status

Overall Survival Across the MONALEESA Phase III Trials

Only KISQALI—a proven first-line overall survival benefit, with preserved quality of life, across all 3 phase III trials
mOS data across the MONALEESA trials

1L refers to patients with mBC.

MONALEESA-2, a dedicated 1L randomized, double-blind, placebo-controlled phase III postmenopausal trial studying KISQALI + letrozole (n=334) vs placebo + letrozole (n=334) in postmenopausal patients with HR+/HER2- mBC who received no prior therapy for advanced disease: At a median follow-up of 80 months, median OS was 63.9 months with KISQALI + letrozole (95% CI: 52.4-71.0) vs 51.4 months with letrozole (95% CI: 47.2-59.7); HR=0.765 (95% CI: 0.628-0.932); P=0.004. In the primary analysis at a median follow-up of 15 months, mPFS was not reached (95% CI: 19.3-NR) vs 14.7 months (95% CI: 13.0-16.5); HR=0.556 (95% CI: 0.429-0.720); P<0.0001. OS was a secondary end point; PFS was the primary end point. At a median follow-up of 26 months, median TTD ≥10% was 27.7 months vs 27.6 months (HR=0.944 [95% CI: 0.720-1.237]).3,4,9-11

MONALEESA-7, a dedicated 1L randomized, double-blind, placebo-controlled phase III premenopausal trial studying 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. At a median follow-up of 54 months (exploratory analysis), median OS was 58.7 months with KISQALI + NSAI + goserelin (95% CI: 48.5-NR) vs 47.7 months with NSAI + goserelin (95% CI: 41.2-55.4); HR=0.798 (95% CI: 0.615-1.035). At a median follow-up of 35 months, superiority was established for overall survival in the ITT population; HR=0.71 (95% CI: 0.54-0.95); P=0.00973. In the primary analysis at a median follow-up of 19 months, median PFS was 27.5 months (95% CI: 19.1-NR) vs 13.8 months (95% CI: 12.6-17.4); HR=0.569 (95% CI: 0.436-0.743). OS was a secondary end point; PFS was the primary end point. Results from the 54-month analyses 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, median TTD ≥10% was 34.2 months vs 23.3 months (HR=0.69 [95% CI: 0.52-0.91]).5,6,11-13

MONALEESA-3, a dedicated 1L and 2L randomized, double-blind, placebo-controlled phase III postmenopausal trial studying KISQALI + fulvestrant (n=484) vs placebo + fulvestrant (n=242) for the treatment of postmenopausal patients with HR+/HER2- mBC who have received no or only 1 line of prior ET for advanced disease: At a median follow-up of 71 months (exploratory analysis), in a 1L subgroup analysis, median OS was 67.6 months (95% CI: 59.6-NR) with KISQALI + fulvestrant vs 51.8 months with placebo + fulvestrant (95% CI: 40.4-61.2); HR=0.673 (95% CI: 0.504-0.899).  At a median follow-up of 39 months, statistical significance was established for overall survival in the ITT population; HR=0.724 (95% CI: 0.568-0.924); P=0.00455. In the primary analysis at a median follow-up of 20 months, median PFS was 20.5 months (95% CI: 18.5-23.5) vs 12.8 months (95% CI: 10.9-16.3); HR=0.593 (95% CI: 0.480-0.732); P<0.0001. At a median follow-up of 39 months, median TTD ≥10% was 35.9 months vs 33.1 months; HR=0.81 (95% CI: 0.62-1.06) OS was a secondary end point; PFS was the primary end point. Results from the 56-month analyses were not prespecified and were observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error. 7,8,11,14,15

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.6,8,16

  • 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 disease17

Dr Gabriel Hortobagyi discusses proven overall survival with KISQALI across 3 phase III trials

 

For information about KISQALI + AI 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; NR=not reached; NSAI=nonsteroidal aromatase inhibitor; OS=overall survival; PFS=progression-free survival; QOL=quality of life; TTD=time to deterioration.

References: 1. Pfizer, Inc. Meaningful goals in the management of mBC. White paper. June 2017. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Published June 21, 2022. Accessed July 29, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. 3. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663 4. Data on file. Novartis Pharmaceuticals Corp; 2017. 5. Data on file. Novartis Pharmaceuticals Corp; 2020. 6. 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 7. Data on file. Novartis Pharmaceuticals Corp; 2022. 8. Fasching PA, Beck JT, Chan A, et al. Ribociclib plus fulvestrant for advanced breast cancer: health-related quality-of-life analyses from the MONALEESA-3 study. Breast. 2020;54:148-154. doi:10.1016/j.breast.2020.09.008 9. Data on file. Novartis Pharmaceuticals Corp; 2021. 10. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738-1748. 11. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 12. 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 13. 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. doi:10.1016/S1470-2045(18)30292-4 14. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465-2472. 15. Slamon DJ, Neven P, Chia S, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149 16. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738-1748;(protocol). doi:10.1056/NEJMoa1609709 17. 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.