Prescribing information

 

Safety profile of KISQALI from three phase III trials.

KISQALI has a consistent and manageable safety profile1

In phase III clinical trials, the majority of AEs were predictable, manageable and reversible.1

AEs observed in the three phase III clinical trials1

 

Table showing the very common and common AEs observed with KISQALI in the three phase III clinical trials

  • Neutropenia was the most common AE across the three phase III trials (MONALEESA-7, MONALEESA-3 and MONALEESA-2)     
    • Neutropenia of any grade was reported in 73.7% of patients receiving KISQALI plus any combination     
    • Grade 3 or 4 neutropenia was reported in 58.6% of patients receiving KISQALI plus any combination
  • Among patients who had grade 2, 3 or 4 neutropenia, the median time to onset was 16 days
  • In the KISQALI plus any combination arms, median time to resolution of grade ≥3 neutropenia (to normalisation or grade <3) was 12 days following treatment interruption and/or reduction and/or discontinuation
  • Febrile neutropenia was reported in 1.4% of patients who received KISQALI plus any combination
  • Less than 1% (0.8%) of patients discontinued KISQALI due to neutropenia
  • Grade 3 or 4 increases in ALT (9.7% vs 1.5%) and AST (6.7% vs 2.1%) were reported in the KISQALI and placebo arms, respectively
  • Among patients who had grade 3 or 4 ALT/AST elevation, median time to onset was 85 days and median time to resolution (to normalisation or grade ≤2) was 22 days for the KISQALI plus any combination arms
  • Concurrent elevations in ALT or AST >3 x ULN and total bilirubin >2 x ULN, with normal alkaline phosphatase, in the absence of cholestasis occurred in 6/1065 patients and all patients recovered after discontinuation
  • Discontinuation of KISQALI plus any combination due to abnormal LFTs or hepatotoxicity occurred in 2.3% and 0.4% of patients, respectively
  • Transaminase elevations have been reported with other CDK4/6 inhibitors2,3
  • Across the phase III clinical trials, 14/1065 patients (1.3%) had >500 msec post-baseline QTcF value and 59/1065 patients (5.6%) had a >60 msec increase from baseline in QTcF intervals
  • Among the patients who had QTcF prolongation >480 msec, the median time to onset was 15 days, and these changes were reversible with dose interruption and/or dose reduction
  • There were no reported cases of torsade de pointes

Toxic epidermal necrolysis (TEN) 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.

  • ILD/pneumonitis has been reported with CDK4/6 inhibitors including KISQALI. In the 3 phase III clinical studies (MONALEESA-2 [A2301], MONALEESA-7 [E2301-NSAI] and MONALEESA-3 [F2301]), ILD (any grade 0.3%, including 0.1% grade 3) was reported in the KISQALI treated group, with no cases in the placebo treated group. Pneumonitis was reported in both the KISQALI and the placebo treated groups (any grade 0.4%, with no grade 3 or 4 in either treatment group)
  • Based on the severity of the ILD/pneumonitis, which may be fatal, KISQALI may require dose interruption, reduction or discontinuation
  • 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 summary of product characteristics

*Infections: urinary tract infections, respiratory tract infections, gastroenteritis, sepsis (<1%).1
Abdominal pain: abdominal pain, abdominal pain upper.1
Rash: rash, rash maculopapular, rash pruritic.1
§Abnormal LFTs: ALT increased, AST increased, blood bilirubin increased.1
**Hepatotoxicity: hepatocellular injury, drug-induced liver injury (<1%), hepatotoxicity, hepatic failure, autoimmune hepatitis (single case).1

Indication: 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 in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.1

AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CDK4/6, cyclin-dependent kinases 4/6; LFT, liver function test; QTcF, QT interval corrected by Fridericia’s formula; ULN, upper limit of normal.

References

  1. KISQALI® (ribociclib) Summary of Product Characteristics.
  2. Ibrance® (palbociclib) Summary of Product Characteristics.
  3. Verzenios® (abemaciclib) Summary of Product Characteristics.
HCP20-C014(1) August 2020.
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Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at http://www.report.novartis.com/
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]