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Safety profile
KISQALI® (ribociclib) safety profile in aBC
Indication:1
KISQALI is indicated for the treatment of women with hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer (aBC) in combination with an aromatase inhibitor (AI) or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy (ET)
In pre- or perimenopausal women, the ET should be combined with a luteinising hormone-releasing hormone (LHRH) agonist
KISQALI is not recommended to be used in combination with tamoxifen.
Please consult your local Summary of Product Characteristics (SmPC) for the full KISQALI safety and tolerability profile and guidance regarding managing adverse events (AEs).
An established safety profile with KISQALI + ET1
KISQALI is not recommended to be used in combination with tamoxifen.1
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The most common AEs in aBC pooled analysis (reported at a frequency ≥20%) were neutropenia, infections, nausea, fatigue, diarrhoea, leukopenia, vomiting, headache, constipation, alopecia, cough, rash, back pain, anaemia and abnormal liver function tests (LFTs)1
Corresponding frequency category for each AE based on the CIOMS III: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from the available data).1
ADVERSE REACTION IN aBC POOLED ANALYSIS | FREQUENCY |
Infections and infestations | |
Infections* | Very common |
Blood and lymphatic system disorders | |
Neutropenia, leukopenia, anaemia, lymphopenia | Very common |
Thrombocytopenia, febrile neutropenia | Common |
Metabolism and nutrition disorders | |
Decreased appetite | Very common |
Hypocalcaemia, hypokalaemia, hypophosphataemia | Common |
Nervous system disorders | |
Headache, dizziness | Very common |
Vertigo | Common |
Eye disorders | |
Lacrimation increased, dry eye | Common |
Cardiac disorders | |
Syncope | Common |
Respiratory, thoracic and mediastinal disorders | |
Dyspnoea, cough | Very common |
Interstitial lung disease (ILD)/pneumonitis | Common |
ADVERSE REACTION IN aBC POOLED ANALYSIS | FREQUENCY |
Gastrointestinal disorders | |
Nausea, diarrhoea, vomiting, constipation, stomatitis, abdominal pain,† dyspepsia | Very common |
Dysgeusia | Common |
Hepatobiliary disorders | |
Hepatotoxicity‡ | Common |
Skin and subcutaneous tissue disorders | |
Alopecia, rash,§ pruritus | Very common |
Erythema, dry skin, vitiligo | Common |
Erythema multiforme | Rare |
Toxic epidermal necrolysis (TEN) | Not known |
Musculoskeletal and connective tissue disorders | |
Back pain | Very common |
General disorders and administration site conditions | |
Fatigue, peripheral oedema, asthenia, pyrexia | Very common |
Dry mouth, oropharyngeal pain | Common |
Investigations | |
Abnormal LFTs¶ | Very common |
Blood creatinine increased, electrocardiogram QT prolonged | Common |
Adapted from KISQALI® Summary of Product Characteristics.1
In aBC, permanent discontinuation was reported in 8.7% of patients receiving KISQALI + ET in Phase III clinical trials.1
For further safety profile information, please refer to the Summary of Product Characteristics.1
KISQALI is not recommended to be used in combination with tamoxifen.1
Pooled safety profile data of AEs of special interest (AESI), across MONALEESA-2, -3 and -7 studies2
| Pooled safety profileǁ | |
Exposure-adjusted any-grade AESI | n (incidence rate per 100 patient-treatment years)** | |
KISQALI + ET (n=1065) | Placebo + ET (n=818) | |
Any AESI | 992 (561.4) | 543 (131.0) |
Neutropenia | 788 (196.6) | 43 (5.1) |
Leukopenia | 330 (34.9) | 36 (4.2) |
Anaemia | 200 (18.2) | 51 (5.9) |
Increased ALT | 161 (13.8) | 48 (5.7) |
Increased AST | 150 (12.7) | 51 (6.0) |
Prolonged ECG QT | 69 (5.6) | 13 (1.5) |
Adapted from Tripathy D, et al. 2019.2
There were no new safety signals reported for KISQALI across follow-up OS analyses of the MONALEESA trials3–5
KISQALI is not recommended to be used in combination with tamoxifen.1
Please see the respective Summary of Product Characteristics for further information on dose modifications and adjustments.
Contraindications1
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Hypersensitivity to the active substance or to peanut, soya or any of the excipients listed in the SmPC.
Special warnings and precautions for use1
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Critical visceral disease
The efficacy and safety of KISQALI have not been studied in patients with critical visceral disease.
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Neutropenia
Based on the severity of the neutropenia, treatment with KISQALI may have to be interrupted, reduced or discontinued.
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Hepatobiliary toxicity
LFTs should be performed before initiating treatment with KISQALI. After initiating treatment, liver function should be monitored.
Based on the severity of the transaminase elevations, treatment with KISQALI may have to be interrupted, reduced or discontinued. Recommendations for patients who have elevated AST/ALT grade ≥3 at baseline have not been established.
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QT interval prolongation
ECG should be assessed before initiating treatment. Treatment with KISQALI should be initiated only in patients with QTcF values <450 msec. ECG should be repeated at approximately Day 14 of the first cycle, then as clinically indicated.
Appropriate monitoring of serum electrolytes (including potassium, calcium, phosphorus and magnesium) should be performed before initiating treatment, at the beginning of the first 6 cycles and then as clinically indicated. Any abnormality should be corrected before initiating treatment with KISQALI and during treatment with KISQALI.
The use of KISQALI should be avoided in patients who already have or who are at significant risk of developing QTc prolongation. This includes patients:
with long QT syndrome
with uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmias
with electrolyte abnormalities
The use of KISQALI with medicinal products known to prolong QTc interval and/or strong cytochrome P450 3A4 (CYP3A4) inhibitors should be avoided as this may lead to clinically meaningful prolongation of the QTcF interval. If treatment with a strong CYP3A4 inhibitor cannot be avoided, the dose should be reduced to 400 mg once daily. Based on the observed QT prolongation during treatment, treatment with KISQALI may have to be interrupted, reduced or discontinued.
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Severe cutaneous reactions
Toxic epidermal necrolysis has been reported with KISQALI treatment. If signs and symptoms suggestive of severe cutaneous reactions (e.g., progressive widespread skin rash often with blisters or mucosal lesions) appear, KISQALI should be discontinued immediately.
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Interstitial lung disease (ILD)/pneumonitis
ILD/pneumonitis is a common AE associated with KISQALI. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis, which may include hypoxia, cough and dyspnoea, and dose modifications should be managed in accordance with the SmPC. Based on the severity of the ILD/pneumonitis, which may be fatal, KISQALI may require dose interruption, reduction or discontinuation.
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Blood creatine increase
KISQALI may cause blood creatinine increase as an inhibitor of the renal transporters organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1), which are involved in the active secretion of creatinine from the proximal tubules. In case of blood creatinine increase while on treatment, it is recommended that further assessment of the renal function be performed to exclude renal impairment.
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CYP3A4 substrates
KISQALI is a strong CYP3A4 inhibitor at the 600 mg dose and a moderate CYP3A4 inhibitor at the 400 mg dose. Thus, KISQALI may interact with medicinal products which are metabolised via CYP3A4, which may lead to increased serum concentrations of CYP3A4 substrates. Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index, and the SmPC of the other product should be consulted for the recommendations regarding co-administration with CYP3A4 inhibitors.
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Renal impairment
The recommended starting dose of 200 mg for patients with severe renal impairment is estimated to result in approximately 45% lower exposure compared with the standard starting dose in patients with normal renal function. The efficacy at this starting dose has not been studied. Caution should be used in patients with severe renal impairment, with close monitoring for signs of toxicity.
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Women of childbearing potential
Pregnancy status should be verified prior to starting treatment with KISQALI. Women of childbearing potential should be advised to use an effective method of contraception while taking KISQALI and for at least 21 days after the last dose.
Pregnancy: KISQALI is not recommended during pregnancy and in women of childbearing potential not using contraception.
Breastfeeding: Patients receiving KISQALI should not breastfeed for at least 21 days after the last dose.
Fertility: There are no clinical data available regarding the effects of KISQALI on fertility. Based on animal studies, KISQALI may impair fertility in males of reproductive potential.
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Soya lecithin
KISQALI contains soya lecithin. Patients who are hypersensitive to peanut or soya should not take KISQALI.
Safety profile in the MONALEESA-2 study
KISQALI + AI was generally well tolerated, with neutropenia, leukopenia and abnormal LFTs as the most common grade 3/4 AEs††6
| KISQALI + AI | PLACEBO + AI |
Dose reductions due to AEs, % (n) | 54.5 (182) | 4.2 (14) |
Discontinuations due to AEs, % (n) | 8.1 (27) | 2.4 (8) |
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % | Neutropenia, 76.9; nausea, 53.3; fatigue, 41.3; diarrhoea, 38.3; alopecia, 34.4; vomiting, 33.5; arthralgia, 33.2; leukopenia, 32.9; constipation, 27.8; headache, 26.9; hot flushes, 24.6; back pain, 24.3; cough, 23.1; rash, 22.2; anaemia, 21.3; decreased appetite, 20.7; abnormal LFTs, 20.1 | Neutropenia, 5.8; nausea, 30.6; fatigue, 32.4; diarrhoea, 24.5; alopecia, 16.1; vomiting, 16.7; arthralgia, 32.7; leukopenia, 4.5; constipation, 21.5; headache, 20.9; hot flushes, 25.5; back pain, 20.3; cough, 21.2; rash, 8.8; anaemia, 5.8; decreased appetite, 15.8; abnormal LFTs, 6.4 |
Most common grade 3 or 4 AEs (≥5%) in the KISQALI arm, % | Neutropenia, 62.0; leukopenia, 21.3; abnormal LFTs, 10.2 | Neutropenia, 1.2; leukopenia, 0.9; abnormal LFTs, 2.4 |
Adapted from Hortobagyi GN, et al. 2018.6
In the MONALEESA-2 protocol-specified final analysis of overall survival (OS), no new safety signals were observed at a median follow-up of 80 months.3
MONALEESA-2: N=668, double-blind, placebo-controlled, 1:1 randomisation, multicentre, Phase III trial in postmenopausal women with HR+/HER2− aBC. As 1L in advanced disease and no prior ET for aBC. KISQALI 600 mg or placebo orally once daily (3 weeks on/1 week off) + AI (letrozole 2.5 mg continuous).7
The primary endpoint was locally assessed progression-free survival (PFS)7
The key secondary endpoint was OS7
Other secondary endpoints included the overall response rate (ORR, complete or partial response), the clinical benefit rate (CBR, overall response plus stable disease lasting 24 weeks or more), safety, and quality-of-life assessments7
Safety profile in the MONALEESA-3 study
The most frequent AEs in postmenopausal HR+/HER2− aBC patients in MONALEESA-3 were neutropenia, nausea and fatigue‡‡8
| KISQALI + FULVESTRANT | PLACEBO + FULVESTRANT |
Dose reductions due to AEs, % (n) | 33.1 (160) | 3.3 (8) |
Discontinuations due to AEs, % (n) | 8.5 (41) | 4.1 (10) |
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % | Neutropenia, 69.6; nausea, 45.3; fatigue, 31.5; diarrhoea, 29.0; leukopenia, 28.4; vomiting, 26.7; constipation, 24.8; arthralgia, 24.0; cough, 21.7; headache, 21.5 | Neutropenia, 2.1; nausea, 28.2; fatigue, 33.2; diarrhoea, 20.3; leukopenia, 1.7; vomiting, 12.9; constipation, 11.6; arthralgia, 26.6; cough, 15.4; headache, 20.3 |
Most common grade 3 or 4 AEs (≥5%) in the KISQALI arm, % | Neutropenia, 53.4; leukopenia, 14.1 | Neutropenia, 0; leukopenia, 0 |
Adapted from Slamon DJ, et al. 2018.8
In a MONALEESA-3 exploratory analysis, there were no new safety signals detected at a median follow-up of 56 months in HR+/HER2− postmenopausal women with aBC treated with KISQALI + fulvestrant.5
MONALEESA-3: N=726, double-blind, placebo-controlled, 2:1 randomisation, Phase III trial. As 1L and 2L in advanced disease + those with early relapse in postmenopausal women with HR+/HER2− aBC. KISQALI 600 mg or placebo orally once daily (3 weeks on/1 week off) + 500 mg fulvestrant (administered intramuscularly on Day 1 of each 28-day cycle, with an additional dose on Day 15 of cycle 1).8
The primary endpoint was locally assessed PFS8
Secondary endpoints included OS, ORR, CBR, and safety and tolerability8
Analyses were performed in the following subgroups:8
Patients receiving 1L therapy
Patients receiving 2L therapy plus those with early relapse (within 12 months after completion of adjuvant or neoadjuvant ET)
Safety profile in the MONALEESA-7 study
In MONALEESA-7, the majority of the AEs in pre/perimenopausal HR+/HER− aBC patients were generally manageable with dose modifications and a few treatment discontinuations occurred due to AEs§§9
| KISQALI + AI + LHRH AGONIST | PLACEBO + AI + LHRH AGONIST |
Dose reductions due to AEs, % (n) | 31 (104) | 5 (17) |
Discontinuations due to AEs, % (n) | ALT increase 2 (7), AST increase 1 (4), drug-induced liver injury 1 (3), prolonged QTcF <1 (1) | ALT increase 0 (0), AST increase <1 (1), drug-induced liver injury <1 (1), prolonged QTcF 1 (2) |
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % | Neutropenia, 76; hot flush, 34; nausea, 32; leukopenia, 31; arthralgia, 30; fatigue, 23; headache, 23; anaemia, 21; diarrhoea, 20 | Neutropenia, 8; hot flush, 34; nausea, 19; leukopenia, 5; arthralgia, 27; fatigue, 25; headache, 24; anaemia, 10; diarrhoea, 18 |
Most common grade 3 or 4 AEs (≥10%) in the KISQALI arm, % | Neutropenia, 61; leukopenia, 14¶¶ | Neutropenia, 4; leukopenia, 1 |
Adapted from Tripathy D, et al. 2018.9
MONALEESA-7: N=672, double-blind, placebo-controlled, 1:1 randomisation, Phase III trial in pre/perimenopausal women with HR+/HER2− aBC. As 1L in advanced disease and in patients who received 1 or fewer lines of chemotherapy for aBC. KISQALI 600 mg or placebo orally once daily (3 weeks on/1 week off) + AI (letrozole 2.5 mg or anastrozole 1 mg) or tamoxifen 20 mg orally once daily continuously (KISQALI is not recommended to be used in combination with tamoxifen) + LHRH agonist (goserelin 3.6 mg subcutaneously on Day 1 of every cycle).10
The primary endpoint was investigator-assessed PFS10
The key secondary endpoint was OS, defined as the time from randomisation to death from any cause10
Other secondary endpoints included: proportion of patients who achieved an objective response, CBR, time to response, duration of response, time to definitive deterioration of ECOG performance status from baseline, time to 10% deterioration of EORTC QLQ-C30 and safety9
Safety profile in the CompLEEment-1 study
The MONALEESA trials safety profile findings were supported by evidence from the CompLEEment-1 study‖‖11
| KISQALI + AI |
Dose reductions due to AEs, % (neutropenia, ALT increased, AST increased, QTcF prolongation) | 21.4 |
Discontinuations due to AEs, % | 16.3 |
Any grade AEs observed in ≥20% of patients | Neutropenia, 74.5; nausea, 35.9; leukopenia, 27.3; fatigue, 23.4; diarrhoea, 21.3; arthralgia, 20.9; vomiting, 20.0 |
Grade 3 or 4 haematologic abnormalities and biochemical abnormalities (>5%), % | Neutropenia, 57.2; leukopenia, 10.6; increased ALT 7.7; increased AST 5.7 |
Adapted from De Laurentiis M, et al. 2021.11
CompLEEment-1: N=3246, Phase IIIb, single arm, open-label study in men and women (any menopausal status) with HR+/HER2− aBC;11 KISQALI is not licensed for use in men with aBC.1 In 1L setting for advanced disease. 1L of prior CT therapy permitted for aBC. Patients received KISQALI 600 mg once daily (3 weeks on/1 week off) + AI 2.5 mg once daily. Men and premenopausal women received concomitant goserelin (3.6 mg subcutaneous implant every 28 days).11
Primary endpoints were safety and tolerability11
Secondary endpoints included time to progression, ORR, CBR and patient-reported outcomes11
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*Infections: urinary tract infections, respiratory tract infections, gastroenteritis, sepsis (<1%).1
†Abdominal pain: abdominal pain, abdominal pain upper.1
‡Hepatotoxicity: hepatic cytolysis, hepatocellular injury, drug-induced liver injury (<1%), hepatotoxicity, hepatic failure, autoimmune hepatitis.1
§Rash: rash, rash maculopapular, rash pruritic.1
¶Abnormal LFTs: ALT increased, AST increased, blood bilirubin increased.1
ǁThis pooled study includes the full population of MONALEESA-2, the 1L ET subset of MONALEESA-3 and the NSAI subset of MONALEESA-7.2
**The exposure-adjusted incidence rate is the number of patients with an event divided by the corresponding sum of the exposure duration for all patients. Duration of exposure in patient-treatment years is counted to the first qualifying event (or duration of exposure to study treatment for patients without an event).2
††Results from a second interim analysis at a median duration of follow-up of 26.4 months.6
‡‡Results from the first interim analysis. Median time from random assignment to data cut-off was 20.4 months.8
§§Results from the primary analysis at a median follow-up of 19.2 months.9
¶¶In the MONALEESA-7 full safety set, grade 3/4 increased ALT was reported in 5% of patients in the KISQALI arm.9
‖‖Mean duration of follow-up was 25.4 months.11
1L, first-line; 2L, second-line; aBC, advanced or metastatic breast cancer; AE, adverse event; AESI, adverse event of special interest; AI, aromatase inhibitor; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBR, clinical benefit rate; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; CIOMS, Council for International Organizations of Medical Sciences; CT, chemotherapy; CYP3A4, cytochrome P450 3A4; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer core quality of life questionnaire; ET, endocrine therapy; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; ILD, interstitial lung disease; LFT, liver function test; LHRH, luteinising hormone-releasing hormone; NSAI, non-steroidal aromatase inhibitor; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; QTcF, corrected QT interval by Fredericia’s formula; SmPC, summary of product characteristics.
References
KISQALI® (ribociclib) Summary of Product Characteristics. Available at: www.medicines.ie.
Tripathy D, et al. Poster 166P. European Society for Medical Oncology. 2–4 May 2019, Berlin, Germany.
Hortobagyi GN, et al. N Engl J Med 2022;386(10):942–950 and supplementary data.
Lu Y-S, et al. Clin Cancer Res 2022;28:851–859.
Slamon DJ, et al. Ann Oncol 2021;32(8):1015–1024.
Hortobagyi GN, et al. Ann Oncol 2018;29:1541–1547.
Hortobagyi GN, et al. N Engl J Med 2016;375(18):1738–1748.
Slamon DJ, et al. J Clin Oncol 2018;36(24):2465–2472.
Tripathy D, et al. Lancet Oncol 2018;19(7):904–915.
Im S-A, et al. N Engl J Med 2019;381(4):307–316 and supplementary data.
De Laurentiis M, et al. Breast Cancer Res Treat 2021;189(3):689–699.
IE11636720 | May 2026
