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KISQALI® (ribociclib) safety profile in eBC
Indication:1
KISQALI, in combination with an aromatase inhibitor (AI), is indicated for the adjuvant treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative eBC at high risk of recurrence (see section 5.1 of the SmPC for selection criteria).
In pre- or perimenopausal women, or in men, the AI should be combined with a luteinising hormone-releasing hormone (LHRH) agonist
Please consult your local Summary of Product Characteristics (SmPC) for the full KISQALI safety and tolerability profile.
KISQALI 400 mg has a generally manageable and well characterised safety profile1–4
NATALEE study design: (N=5101) international, randomised, multicentre, open-label, Phase III trial in patients with HR+/HER2– eBC. Premenopausal and postmenopausal women, and men with stage IIB, stage IIA (that is either: N1 or N0 high risk), or stage III disease with an initial diagnosis ⩽18 months prior to randomisation were eligible. Patients receiving standard (neo)adjuvant endocrine therapy (ET) were eligible if treatment was initiated ⩽12 months before randomisation. Patients were randomised to receive either KISQALI 400 mg/day plus NSAI or NSAI alone. The primary endpoint was invasive disease-free survival as per Standardised Definitions for Efficacy Endpoints (STEEP) criteria version 1.0, assessed by the investigator.2,3
In an exploratory analysis at 4 years, KISQALI 400 mg had a generally manageable and well characterised safety profile with no new safety signals identified after extended follow-up2
NATALEE adverse events (AEs) at 4 years (exploratory analysis)2
| KISQALI + NSAI (n=2526) | NSAI (n=2441) | ||
AEIS, % | Any grade | Grade ≥3 | Any grade | Grade ≥3 |
Neutropenia* | 62.8 | 44.4 | 4.5 | 0.9 |
Febrile neutropenia | 0.3 | 0.3 | 0.0 | 0.0 |
Liver-related AEs† | 26.7 | 8.6 | 11.4 | 1.7 |
QT interval prolongation‡ | 5.4 | 1.0 | 1.6 | 0.7 |
ECG QT prolonged | 4.4 | 0.2 | 0.8 | <0.1 |
Interstitial lung disease (ILD)/pneumonitis§ | 1.6 | 0.0 | 0.9 | 0.1 |
Other clinically relevant AEs, % | ||||
Arthralgia | 38.8 | 1.0 | 44.4 | 1.3 |
Nausea | 23.5 | 0.2 | 7.9 | <0.1 |
Headache | 22.9 | 0.4 | 17.2 | 0.2 |
Fatigue | 22.8 | 0.8 | 13.5 | 0.2 |
Diarrhoea | 14.6 | 0.6 | 5.5 | 0.1 |
Venous thromboembolism¶ | 1.1 | 0.6 | 0.5 | 0.3 |
Adapted from Fasching PA, et al. 2024.2
KISQALI's tolerability and safety profile is documented as per the SmPC.
Grading according to CTCAE Version 5.0.5
Dose adjustments and discontinuations at 3 years3
| KISQALI + NSAI | NSAI |
KISQALI discontinuation due to AEs | 19.5% | N/A |
NSAI discontinuation due to AEs | 5.1% | 4.4% |
Dose reduction of KISQALI due to AEs | 22.8% | N/A |
Most frequent any-grade AE leading to discontinuation | 9.9% Liver-related‖ | 0.1% Liver-related |
Adapted from Hortobagyi GN, et al. 2025.3
In the KISQALI + NSAI arm, rates of discontinuation due to AEs were consistent and remained stable at 4 years (20.0%), with a <1.0% increase from the 3-year final analysis2
AEs generally occurred early in treatment, allowing for prompt dose adjustments4
For KISQALI, median time to discontinuation due to AEs was 4.17 months (range: 0.10–35.75 months)4
The majority of grade ≥3 AEs were laboratory findings that were generally identifiable and manageable4
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The most common AEs (reported at a frequency ≥20%) in the dataset for which the frequency for KISQALI + AI exceeds the frequency for AI alone were neutropenia, infections, nausea, headache, fatigue, leukopenia and abnormal liver function tests. The most common grade 3/4 adverse drug reactions (reported at a frequency of ≥2%) in the dataset for which the frequency for KISQALI + AI exceeds the frequency for AI alone were neutropenia, abnormal liver function tests and leukopenia.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
AEs in patients with eBC with starting dose of 400 mg KISQALI
AEs | FREQUENCY |
Infections and infestations | |
Infections** | Very common |
Blood and lymphatic system disorders | |
Neutropenia, leukopenia | Very common |
Anaemia, thrombocytopenia, lymphopenia | Common |
Febrile neutropenia | Uncommon |
Metabolism and nutrition disorders | |
Hypocalcaemia, hypokalaemia, appetite decreased | Common |
Nervous system disorders | |
Headache | Very common |
Dizziness | Common |
Respiratory, thoracic and mediastinal disorders | |
Cough | Very common |
Dyspnoea, ILD/pneumonitis | Common |
AEs | FREQUENCY |
Gastrointestinal disorders | |
Nausea, diarrhoea, constipation, abdominal pain†† | Very common |
Vomiting, stomatitis‡‡ | Common |
Hepatobiliary disorders | |
Hepatotoxicity§§ | Common |
Skin and subcutaneous tissue disorders | |
Alopecia | Very common |
Rash,¶¶ pruritus | Common |
General disorders and administration site conditions | |
Fatigue, asthenia, pyrexia | Very common |
Peripheral oedema, oropharyngeal pain | Common |
Investigations | |
Abnormal liver function tests∥∥ | Very common |
Blood creatinine increased, ECG QT prolonged | Common |
Adapted from KISQALI® Summary of Product Characteristics.1
For further safety profile information, please refer to the SmPC.1
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. Complete blood counts should be performed before initiating treatment with KISQALI. After initiating treatment, blood cells/platelet levels should be monitored.
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Hepatobiliary toxicity
Liver function tests 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 as described in the SmPC. 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 with KISQALI in all patients. Treatment with KISQALI should be initiated only in patients with QTcF values less than 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
Uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmias
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 co-administration of KISQALI with a strong CYP3A4 inhibitor cannot be avoided, the KISQALI dose should be changed as described in the SmPC.
Based on the observed QT prolongation during treatment, treatment with KISQALI may have to be interrupted, reduced or discontinued.
KISQALI is not recommended to be used with tamoxifen.
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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 has been reported 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, as described in the SmPC.
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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 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
No dose adjustment is necessary in patients with mild or moderate renal impairment. A starting dose of 200 mg is recommended in patients with severe renal impairment. This recommendation is estimated to result in approximately 45% lower exposure compared with the standard starting dose of 600 mg in advanced or metastatic breast cancer 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 stopping treatment with KISQALI.
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.
Find out more about the safety profile of KISQALI in aBC
Click here to learn more about dosing and monitoring with KISQALI
*Grouped term that combines neutropenia and neutrophil count decreased.2
†Grouped term that includes all preferred terms identified by standardised MedDRA queries for drug-related hepatic disorders.2
‡Grouped term.2
§Grouped term that includes all preferred terms identified by standardised MedDRA queries for ILD.2
¶Grouped term that includes all preferred terms identified by standardised MedDRA queries for venous thromboembolism.2
‖Liver-related: ALT increase 7.1%, AST increase 2.8%.3
**Infections: urinary tract infections, respiratory tract infections, gastroenteritis (only in patients with advanced or metastatic breast cancer), sepsis (<1% only in patients with advanced or metastatic breast cancer).1
††Abdominal pain: abdominal pain, abdominal pain upper.1
‡‡Stomatitis for eBC includes: stomatitis, mucositis.1
§§Hepatotoxicity: hepatic cytolysis, hepatocellular injury (only in patients with advanced or metastatic breast cancer), drug-induced liver injury (<1% in patients with eBC and in patients with advanced or metastatic breast cancer), hepatotoxicity, hepatic failure (only in patients with advanced or metastatic breast cancer), autoimmune hepatitis.1
¶¶Rash: rash, rash maculopapular, rash pruritic.1
‖‖Abnormal liver function tests: ALT increased, AST increased, blood bilirubin increased.1
AE, adverse event; AEIS, adverse event of special interest; AI, aromatase inhibitor; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CIOMS, Council for International Organizations of Medical Sciences; CTCAE, common terminology criteria for adverse events; CYP3A4, cytochrome P450 3A4; eBC, early breast cancer; ECG, electrocardiogram; ET, endocrine therapy; HER2, human epidermal growth factor receptor; HR, hormone receptor; ILD, interstitial lung disease; LHRH, luteinising hormone-releasing hormone; MATE1, multidrug and toxin extrusion protein 1; MeDRA, Medical Dictionary for Regulatory Activities; N/A, not applicable; NSAI, non-steroidal aromatase inhibitor; OCT2, organic cation transporter 2; QTcF, corrected QT interval by Fridericia’s formula; SmPC, summary of product characteristics; STEEP; standardised definitions for efficacy endpoints.
References
KISQALI® (ribociclib) Summary of Product Characteristics. Available at www.medicines.ie.
Fasching PA, et al. Oral LBA13. European Society for Medical Oncology Congress, 13–17 September 2024, Barcelona, Spain.
Hortobagyi GN, et al. Ann Oncol 2025;36(2):149–157.
Barrios C, et al. Oral presentation 113MO. European Society for Medical Oncology Breast Cancer Congress, 15–17 May 2024, Berlin, Germany.
National Cancer Institute. Common terminology criteria for adverse events (CTCAE) v5.0. 2017. Available at: https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v5-5x7.pdf [Accessed April 2026].
IE11637377 | April 2026
