Prescribing information

 

KISQALI has a consistent and manageable safety profile1–11

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In MONALEESA-7, the majority of adverse events in premenopausal HR+/HER2– aBC patients were reversible with dose modifications, allowing most patients to stay on treatment.1–3,6  

 

  KISQALI + NSAI + LHRH AGONIST

(N=248)
PLACEBO + NSAI + LHRH AGONIST

(N=247)
Dose reductions due to AEs, % (n) 33% (82) 4% (10)
Discontinuations due to AEs, % (n) 7% (17) 3% (7)
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % Neutropenia, 78%; Arthralgia 33%; Hot flushes, 31%; Nausea, 31%; Leukopenia, 30%; Fatigue, 23%; Headache, 23%; Alopecia, 21%; Diarrhoea, 20% Neutropenia, 8%; Arthralgia, 29%; Hot flushes, 30%; Nausea, 20%; Leukopenia, 5%; Fatigue, 25%; Headache, 24%; Alopecia, 13%; Diarrhoea, 19%
Most common grade 3 or 4 AEs (≥5%) in the KISQALI arm, % Neutropenia, 65%; Leukopenia, 16%* N/A

Adapted from Bardia A, et al. 2018.6

 

MONALEESA-7: N=672, double-blind, placebo-controlled, 1:1 randomisation in premonopausal 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 + LHRH agonist (goserelin 3.6 mg subcutaneously on day 1 of every cycle).1,2 The primary endpoint was investigator-assessed progression-free survival. The key secondary endpoint was overall survival, defined as the time from randomisation to death from any cause. The other secondary endpoints included: proportion of patients who achieved clinical benefit, 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 safety.1,3

* In the MONALEESA-7 full safety set, grade 3/4 increased ALT was reported in 5% of patients.3

Very few premenopausal HR+/HER2− aBC patients discontinued treatment because of adverse events in MONALEESA-7*3

 

REASONS FOR

DISCONTINUATION
KISQALI + ET + LHRH AGONIST

(N=335)
PLACEBO + ET + LHRH AGONIST

(N=337)
Alanine aminotransferase increased, n (%) 7 (2) 0
Aspartate aminotransferase increased, n (%) 4 (1) 1 (<1)
Drug-induced liver injury, n (%) 3 (1) 1 (<1)
Prolonged QTcF, n (%) 1 (<1) 2 (1)

Adapted from Tripathy D, et al. 2018.3

* The most common reasons for discontinuation of any component of study treatment owing to adverse events suspected to be related to study treatment.

† KISQALI is not recommended to be used in combination with tamoxifen.2

KISQALI + letrozole was generally well tolerated, with neutropenia and leukopenia the most common grade 3/4 AEs.*7

 

  KISQALI + letrozole

(N=334)
PLACEBO + letrozole

(N=330)
Dose reductions due to AEs, % 55% 4%
Discontinuations due to AEs, % 8% 2%
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % Neutropenia, 77%; Nausea, 53%; Fatigue, 41%; Diarrhoea, 38%; Alopecia, 34%; Vomiting, 34%; Arthralgia, 33%; Leukopenia, 33%; Constipation, 28%; Headache, 27%; Hot flushes, 25%; Back pain, 24%; Cough, 23%; Rash, 22%; Anemia, 21%; Decreased appetite, 21%; Abnormal LFTs, 20% Neutropenia, 6%; Nausea, 31%; Fatigue, 32%; Diarrhoea, 25%; Alopecia, 16%; Vomiting, 17%; Arthralgia, 33%; Leukopenia, 5%; Constipation, 22%; Headache, 21%; Hot flushes, 26%; Back pain, 20%; Cough, 21%; Rash, 9%; Anemia, 6%; Decreased appetite, 16%; Abnormal LFTs, 6%
Most common grade 3 or 4 AEs (≥5%) in the KISQALI arm, % Neutropenia, 63%; Leukopenia, 21%; Abnormal LFTs, 10% N/A

Adapted from Hortobagyi GN, et al. 2018.7

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 endocrine therapy for aBC. KISQALI 600 mg or placebo orally once daily (3 weeks on/1 week off) + AI (letrozole 2.5 mg continuous).8 The primary endpoint was locally assessed progression-free survival and the key secondary endpoint was overall survival. Other secondary endpoints included the overall response rate (complete or partial response), the clinical benefit rate (overall response plus stable disease lasting 24 weeks or more), safety, and quality-of-life assessments.8

* Results from 26.4 month follow-up analysis.7

The most frequent AEs in postmenopausal HR+/HER2− aBC patients in MONALEESA-3 were neutropenia, nausea and fatigue*9

 

  KISQALI + FULVESTRANT

(N=483)
PLACEBO + FULVESTRANT

(N=241)
Dose reductions due to AEs, % (n) 33% (160) 3% (8)
Discontinuations due to AEs, % (n) 9% (43) 4% (9)
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % Neutropenia, 70%; Nausea, 45%; Fatigue, 32%; Diarrhoea, 29%; Leukopenia, 28%; Vomiting, 27%; Constipation, 25%; Arthralgia, 24%; Cough, 22%; Headache, 22% Neutropenia 2%; Nausea, 28%; Fatigue, 33%; Diarrhoea, 20%; Leukopenia, 2%; Vomiting, 13%; Constipation, 12%; Arthralgia, 27%; Cough, 15%; Headache, 20%
Most common grade 3 or 4 AEs (≥5%) in the KISQALI arm, % Neutropenia, 53%;

Leukopenia, 14%
N/A

Adapted from Slamon DJ, et al. 2018.9

In a MONALEESA-3 exploratory analysis, there were no new safety signals detected at a follow-up of ~4.5 years in HR+/HER2− postmenopausal women with aBC treated with KISQALI + fulvestrant.10

MONALEESA-3: N=726, double-blind, placebo-controlled, 2:1 randomisation. As 1L and 2L in advanced disease plus 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.9,10 The primary endpoint was locally assessed progression-free survival. Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate, and safety and tolerability.9 Analyses were performed in the following subgroups:11

  • Patients receiving 1L therapy
  • Patients receiving 2L therapy plus those with early relapse (within 12 months after completion of adjuvant or neoadjuvant endocrine therapy)

* Results from first interim analysis.

The MONALEESA safety findings were supported by evidence from the Compleement-1 study – the largest phase IIIb CDK4/6 inhibitor trial in aBC to date4,5 

 

  KISQALI + LETROZOLE

(N=3246)
Dose reductions due to AEs, % Not reported
Discontinuations due to AEs, % 12.9%
Any grade AEs observed in ≥20% of patients in the KISQALI arm, % Neutropenia, 61.1%; Nausea, 35.9%; Fatigue, 23.4%
Most common grade 3 or 4 AEs (≥5%) in the KISQALI arm, % Not reported

Adapted from De Laurentiis M, et al. 2020.4

Compleement-1: N=3246, Phase IIIb, open-label study in men and women (any menopausal status) with HR+/HER2- aBC. In 1L setting for advanced disease. 1 line of prior CT therapy permitted for aBC. Patients received KISQALI 600 mg once daily (3  weeks on/1 week off) + letrozole 2.5 mg once daily. Primary endpoints were safety and tolerability. Secondary endpoints included time to progression, ORR, CBR and patient reported outcomes.4,5 KISQALI is not licensed for use in men.2

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.2  

1L, first line; 2L, second line; aBC, advanced breast cancer; AE, adverse event; AI, aromatase inhibitor; ALT, alanine aminotransferase; CBR, clinical benefit rate; CDK4/6, cyclin-dependent kinase 4 and 6; CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire; ET, endocrine therapy; HR+/HER2–, hormone receptor-positive/human epidermal growth factor 2-negative; LFT, liver function test; LHRH, luteinising hormone-releasing hormone; ORR, overall response rate; QTcF, QT interval corrected for Fridericia’s formula.

  1. Im S-A, et al. N Engl J Med. 2019;381(4):307–316.
  2. KISQALI (ribociclib). Summary of Product Characteristics.
  3. Tripathy D, et al. Lancet Oncol. 2018;19(7):904–915.
  4. De Laurentiis M, et al. J Clin Oncol. 2020;38(15):1055–1055.
  5. De Laurentiis M, et al. J Clin Oncol. 2018;36(15):1056–1056.
  6. Bardia A, et al. Poster 330P. Presentation at European Society for Medical Oncology Congress, 19–23 October, 2018, Munich, Germany.
  7. Hortobagyi GN, et al. Ann Oncol. 2018;29(7):1541–1547.
  8. Hortobagyi GN, et al. N Engl J Med. 2016;375(18):1738–1748.
  9. Slamon DJ, et al. J Clin Oncol. 2018;36(24):2465–247.
  10. Slamon DJ, et al. Presented at ASCO Annual Meeting, 4–8 June 2021.
  11. Slamon DJ, et al. N Engl J Med. 2020;382(6):514–524.
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
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