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...

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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

Efficacy

NATIONAL COMPREHENSIVE CANCER NETWORK® (NCCN®)
Ribociclib (KISQALI®) is a recommendation in HR+/HER2- mBC for postmenopausal women with an AI, postmenopausal women with fulvestrant, and premenopausal women with an LHRH agonist + an AI—based on evidence from the only dedicated trial in the first-line setting.1,2

Efficacy Across 3 Phase III Trials

Largest body of first-line evidence for a CDK4/6 inhibitor regardless of menopausal status or combination2,3

THE FIRST AND ONLY TRIAL dedicated to premenopausal women in nearly 20 years (n=495)2,4
                       
mPFS

27.5

months
PREMENOPAUSAL
First line
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)2
  • mPFS results based on a prespecified subgroup analysis of 495 patients who received KISQALI® (ribociclib) or placebo with an NSAI + goserelin3
THE LARGEST TRIAL to evaluate a CDK4/6 inhibitor + fulvestrant as initial therapy in postmenopausal women (N=726)2,3
                       
mPFS

20.5

months
POSTMENOPAUSAL
First line and second line
KISQALI + fulvestrant (ITT)
(95% CI: 18.5-23.5) vs 12.8 months with placebo + fulvestrant (95% CI: 10.9-16.3), HR=0.593 (95% CI: 0.480-0.732); P<0.00013
THE LARGEST FIRST-LINE TRIAL to evaluate a CDK4/6 inhibitor + AI in postmenopausal women (N=668)2,3,5
                       
mPFS

25.3

months
POSTMENOPAUSAL
First line
KISQALI + letrozole (ITT)
vs 16.0 months with placebo + letrozole5
  • mPFS results based on a subsequent preplanned OS analysis5
44% reduction in risk of progression or death with KISQALI + letrozole vs placebo + letrozole (HR=0.556 [95% CI: 0.429-0.720]; P<0.0001) (primary end point, interim analysis).3
MONALEESA-7 Study Description

MONALEESA-7 was a randomized, double-blind, placebo-controlled, multicenter, phase III trial in premenopausal women with HR+/HER2- mBC who received no prior endocrine therapy for advanced or metastatic disease. Patients (N=672) were stratified by the presence of liver and/or lung metastases, prior chemotherapy for advanced disease, and endocrine combination partner. Patients were randomized (1:1) to receive either KISQALI 600 mg (3 weeks on, 1 week off), an NSAI (letrozole 2.5 mg or anastrozole 1 mg once daily on a continuous basis) or tamoxifen 20 mg (once daily on a continuous basis), and goserelin 3.6 mg (monthly subcutaneous injection) or placebo (3 weeks on, 1 week off), an NSAI (letrozole 2.5 mg or anastrozole 1 mg once daily on a continuous basis) or tamoxifen 20 mg (once daily on a continuous basis), and goserelin 3.6 mg (monthly subcutaneous injection). The primary end point was PFS using RECIST v1.1; secondary end points included OS, ORR, QOL, and safety. The efficacy and safety results presented are from a prespecified subgroup analysis of 495 patients who had received KISQALI or placebo with an NSAI plus goserelin.3,4

MONALEESA-3 Study Description

MONALEESA-3 was a randomized, double-blind, placebo-controlled, multicenter, phase III trial in postmenopausal women with HR+/HER2- mBC who received no or only 1 prior line of endocrine therapy for advanced or metastatic disease. Patients (N=726) were stratified by the presence of liver and/or lung metastases and prior endocrine therapy for advanced or metastatic disease. Patients were randomized (2:1) to receive either KISQALI 600 mg (3 weeks on, 1 week off) and fulvestrant 500 mg (intramuscular injection on Days 1, 15, 29, and once monthly thereafter) or placebo (3 weeks on, 1 week off) and fulvestrant 500 mg (intramuscular injection on Days 1, 15, 29, and once monthly thereafter). The primary end point was PFS using RECIST v1.1; secondary end points included OS, ORR, QOL, and safety.3,6,7

MONALEESA-2 Study Description

MONALEESA-2 was a randomized, double-blind, placebo-controlled, multicenter, phase III trial in postmenopausal women with HR+/HER2- mBC who received no prior therapy for advanced disease. Patients (N=668) were stratified by the presence of liver and/or lung metastases and randomized 1:1 to receive either KISQALI 600 mg (3 weeks on, 1 week off) and letrozole 2.5 mg (continuously) or placebo (3 weeks on, 1 week off) and letrozole 2.5 mg (continuously). The primary end point was PFS using RECIST v1.1; secondary end points included OS, ORR, QOL, and safety; exploratory end points included tumor size reduction and DOR.3,8,9

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.

Please see additional Important Safety Information below.

 

1L Results in Premenopausal Women With KISQALI + an NSAI

PREMENOPAUSAL

MONALEESA-7

Rapid and sustained FIRST-LINE efficacy for younger women3

mPFS sustained for nearly 28 months with KISQALI + NSAI3

PFS PER INVESTIGATOR ASSESSMENT (NSAI)3

Line graph showing rapid and sustained efficacy in premenopausal women for 28 months with KISQALI (ribociclib) Line graph showing rapid and sustained efficacy in premenopausal women for 28 months with KISQALI (ribociclib)
  • Efficacy results are based on a prespecified subgroup analysis of 495 patients who received KISQALI or placebo with an NSAI + goserelin3
Rapid separation of the PFS curves evident at 8 weeks3
  • Results reported at 8 weeks were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error
KISQALI + NSAI + goserelin preserved QOL throughout treatment11

During treatment, QOL was maintained from baseline and similar in both arms. There was no significant difference in the TTD of global health status/QOL ≥10% (HR=0.759 [95% CI: 0.561-1.028]). At disease progression or EOT, overall QOL worsened in both arms.10*

Consider the following patient case:
Katherine
  • 35 years old
  • Diagnosed with Stage I HR+/HER2- breast cancer 3 years ago
  • Previous treatments: adjuvant chemotherapy and tamoxifen
  • ECOG PS 1
  • Biopsy confirmed HR+/HER2- metastatic breast cancer
Consistent efficacy in women younger than 40 years old like Katherine10
In a pre-specified subgroup, 57% reduction in risk of progression or death in first-line patients <40 years old (n=144) with KISQALI + NSAI + goserelin vs placebo + NSAI + goserelin (HR=0.434 [95% CI: 0.273-0.691])10

Review more data from the MONALEESA-7 trial to see how patients like Katherine responded.

*The EORTC QLQ-C30 questionnaire was used to assess the secondary QOL PRO end point. The EORTC QLQ-C30 is a standard QOL PRO tool that includes 5 functional scales: physical, role, emotional, cognitive, and social; 3 symptom scales: fatigue, nausea and vomiting, and pain; 6 single items: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties.10
Hypothetical patient profile.

IMPORTANT SAFETY INFORMATION (continued)
QT interval prolongation (continued). 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.

 Please see additional Important Safety Information below.

1L/2L Results in Postmenopausal Women With KISQALI + Fulvestrant

POSTMENOPAUSAL

MONALEESA-3

Rapid and sustained first- and second-line efficacy with KISQALI + fulvestrant3

Superior efficacy demonstrated in first-line and second-line patients with KISQALI + fulvestrant3

PFS PER INVESTIGATOR ASSESSMENT (ITT)3

Line graph showing rapid and sustained efficacy in postmenopausal women for 20.5 months with KISQALI (ribociclib) and fulvestrant Line graph showing rapid and sustained efficacy in postmenopausal women for 20.5 months with KISQALI (ribociclib) and fulvestrant
  • Efficacy results included first-line patients (de novo or progression >12 months after completion of [neo]adjuvant ET) or early adjuvant relapsers (progression ≤12 months after completion of or during [neo]adjuvant ET) and second-line patients (progression following ET in the metastatic setting)6*
  • Results reported at 8 weeks were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error
KISQALI + fulvestrant preserved QOL throughout treatment7

During treatment, QOL was maintained from baseline and similar in both arms. There was no significant difference in the TTD of global health status/QOL ≥10% (HR=0.795 [95% CI: 0.602-1.050]). At disease progression or EOT, overall QOL worsened in both arms.7†

Consider the following patient case:

Isabel

  • Diagnosed with Stage II HR+/HER2- breast cancer 1 year ago
  • Previous treatments: breast-conserving surgery, radiotherapy, and adjuvant letrozole
  • During adjuvant letrozole, developed persistent pain in left leg
  • ECOG PS 0
  • Bone biopsy confirmed HR+/HER2- metastatic breast cancer

Consistent efficacy, including in early adjuvant relapsers like Isabel6

In a pre-specified subgroup, 44% reduction in risk of progression or death in early adjuvant relapsers and second-line patients (n=345) with KISQALI + fulvestrant vs fulvestrant alone (HR=0.565 [95% CI: 0.428-0.744])6

Review more data from the MONALEESA-3 trial to see how patients like Isabel responded.

*First line (de novo or progression >12 months after completion of [neo]adjuvant ET). Early adjuvant relapsers (progression ≤12 months after completion of or during [neo]adjuvant ET) and second line (progression following ET in the metastatic setting).6
The EORTC QLQ-C30 questionnaire was used to assess the secondary QOL PRO end point. The EORTC QLQ-C30 is a standard QOL PRO tool that includes 5 functional scales: physical, role, emotional, cognitive, and social; 3 symptom scales: fatigue, nausea and vomiting, and pain; 6 single items: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties.7
Hypothetical patient profile.

IMPORTANT SAFETY INFORMATION (continued)
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.

Please see additional Important Safety Information below.

1L Results in Postmenopausal Women With KISQALI + an AI

POSTMENOPAUSAL

MONALEESA-2

Rapid and sustained first-line efficacy with KISQALI + letrozole5

PFS PER INVESTIGATOR ASSESSMENT (ITT, SUBSEQUENT PREPLANNED OS ANALYSIS)5
Line graph showing rapid and sustained efficacy in postmenopausal women for 25 months with KISQALI (ribociclib) and an aromatoase inhibitor (AI) Line graph showing rapid and sustained efficacy in postmenopausal women for 25 months with KISQALI (ribociclib) and an aromatoase inhibitor (AI)

44% reduction in risk of progression or death3

  • KISQALI + letrozole vs placebo + letrozole (HR=0.556 [95% CI: 0.429-0.720]; P<0.0001) (primary end point, interim analysis)3
Rapid separation of the PFS curves evident at 8 weeks3
  • Results reported at 8 weeks were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error
KISQALI + letrozole preserved QOL throughout treatment12

During treatment, QOL was maintained from baseline and similar in both arms. There was no significant difference in the TTD of global health status/QOL ≥10% (HR=0.944 [95% CI: 0.720-1.237]). At disease progression or EOT, overall QOL worsened in both arms.12*

Consider the following patient case:

Sandra

  • Diagnosed with Stage I HR+/HER2- breast cancer 8 years ago
  • Previous treatments: lumpectomy, radiotherapy, and adjuvant anastrozole
  • ECOG PS 1
  • Pleural biopsy confirmed HR+/HER2- metastatic breast cancer
  • Metastases in lung, ribs, and liver observed by CT scan

Consistent PFS benefit in women with visceral metastases like Sandra13

PFS in women with visceral disease (n=393)13

In a pre-specified subgroup, mPFS 24.9 months with KISQALI + letrozole (95% CI: 22.2-30.9) vs 13.4 months with placebo + letrozole (95% CI: 12.7-16.5), HR=0.54 (95% CI: 0.41-0.71)13

Review more data from the MONALEESA-2 trial to see how patients like Sandra responded.

*The EORTC QLQ-C30 questionnaire was used to assess the secondary QOL PRO end point. The EORTC QLQ-C30 is a standard QOL PRO tool that includes 5 functional scales: physical, role, emotional, cognitive, and social; 3 symptom scales: fatigue, nausea and vomiting, and pain; 6 single items: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties.12
Hypothetical patient profile.

IMPORTANT SAFETY INFORMATION (continued)
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.

Please see additional Important Safety Information below.

For information about the safety profile, continue to the next page >

AI=aromatase inhibitor; CDK=cyclin-dependent kinase; CT=computed tomography; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30=European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; EOT=end of treatment; ET=endocrine therapy; HER2-=human epidermal growth factor receptor 2-negative; HR=hazard ratio; HR+=hormone receptor-positive; ITT=intent to treat; LHRH=luteinizing hormone-releasing hormone; mBC=metastatic breast cancer; mPFS=median progression-free survival; NR=not reached; NSAI=nonsteroidal aromatase inhibitor; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PRO=patient-reported outcome; QOL=quality of life; RECIST=Response Evaluation Criteria In Solid Tumors; TTD=time to deterioration.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed October 26, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. The National Comprehensive Cancer Network 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. 2. ClinicalTrials.gov. Search results for fulvestrant; combination advanced breast cancer studies; recruiting; not yet recruiting; active, not recruiting, completed, enrolling by invitation, suspended, terminated, withdrawn, unknown status; phase 3; breast cancer; CDK; NCT01942135; NCT02102490. Search conducted July 2018. 3. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 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. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541-1547. 6. 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. 7. Data on file. Novartis Pharmaceuticals Corp; 2018. 8. 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. 9. Janni W, Alba E, Bachelot T, et al. First-line ribociclib plus letrozole in postmenopausal women with HR+, HER2– advanced breast cancer: tumor response and pain reduction in the phase 3 MONALEESA-2 trial. Breast Cancer Res Treat. 2018;169(3):469-479. 10. Beck JT, Wheatley-Price P, Nevin P, et al. Patient-reported outcomes with ribociclib-based therapy in hormone receptor-positive, HER2-negative advanced breast cancer: results from the Phase III MONALEESA-2, -3, and -7 trials. Poster presented at: San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Poster P6-18-14. 11. Tripathy D, Sampos-Gomez S, Lu Y-S, et al. Ribociclib with a nonsteroidal aromatase inhibitor and goserelin in premenopausal women with HR-positive, HER2-negative ABC: MONALEESA-7 age subgroup analysis. Poster presented at: San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Poster P6-18-04. 12. Verma S, O'Shaughnessy J, Burris HA, et al. Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465-2472. 13. Yardley DA, Chan A, Nusch A, et al. Ribociclib plus endocrine therapy in patients with hormone receptor-positive, HER2-negative advanced breast cancer presenting with visceral metastases: subgroup analysis of phase 3 MONALEESA trials. Poster presented at: San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Poster P6-18-07.

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.