Prescribing information

 

KISQALI + ET* is the only CDK4/6i to show statistically significant OS in two phase III trials in the advanced setting1–4

 

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 intramuscular fulvestrant. 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.4

MONALEESA-3 primary endpoint: PFS in the ITT population4

mPFS in the ITT population was 20.5 months in the KISQALI + fulvestrant arm vs 12.8 months in the placebo + fulvestrant arm, HR 0.59 (95% CI: 0.48–0.73) p<0.001.4

 

* KISQALI is not recommended to be used in combination with tamoxifen.3

MONALEESA-3: OS with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal patients (ITT population; N=726; data cutoff 3 June 2019)1

 

 Kaplan-Meier graph for overall survival in MONALEESA-3:  with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal patients (ITT population; N=726; data cutoff 3 June 2019) over 48 months.

Adapted from Slamon DJ, et al. 2020.1

In a sub-analysis of overall survival by line of treatment, patients who received KISQALI + fulvestrant as first-line treatment* (n=237) had an mOS NR vs 45.1 months in the placebo + fulvestrant arm (n=128) (HR 0.70; 95% CI: 0.48–1.02) after a median follow-up of 39.4 months. 

Patients who received KISQALI + fulvestrant as second-line therapy or after early relapse (n=237) had an mOS 40.2 months vs 32.5 months in the placebo + fulvestrant arm (n=109) (HR 0.73; 95% CI: 0.53–1.00).1

KISQALI + fulvestrant is recommended by NICE in the second line setting for the treatment of HR+/HER2− aBC women who have had previous endocrine therapy where appropriate.‡5

* Newly diagnosed (de novo) advanced breast cancer or those who had relapsed >12 months from completion of adjuvant or neoadjuvant endocrine therapy with no treatment for advanced or metastatic disease.6
† Relapse during or within 12 months of completing adjuvant or neoadjuvant endocrine therapy with no treatment for advanced metastatic disease; advanced or metastatic breast cancer at diagnosis that progressed after one line of endocrine therapy for advanced disease with no prior adjuvant or neoadjuvant treatment for early disease; relapse >12 months from completion of adjuvant or neoadjuvant endocrine therapy with subsequent progression after one line of endocrine therapy for advanced or metastatic disease.6
‡ KISQALI + fulvestrant is recommended as an option for treating women with HR+/HER2− aBC who have had previous ET, only if: exemestane + everolimus is the most appropriate alternative to CDK4/6i AND the company provides KISQALI according to the commercial agreement.5

KISQALI + fulvestrant reports the longest median overall survival vs placebo + fulvestrant in an exploratory analysis of a CDK4/6i trial specifically in postmenopausal HR+/HER2 aBC patients*7

The observed overall survival benefit in postmenopausal women with HR+/HER2- aBC was maintained for nearly 4.5 years, with an mOS of 53.7 months.7

MONALEESA-3: OS with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal patients (ITT population; N=726; data cutoff 30 October 2020)7

 

Kaplan-Meier graph for overall survival in MONALEESA-3:  with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal patients (ITT population; N=726; data cutoff 3 June 2019) over 64 months.

Adapted from Slamon DJ, et al. 2021.7

These results are exploratory in nature; as such, there was no prespecified statistical procedure controlling for type 1 error.

* As reported in the ITT population of the MONALEESA-3 extended exploratory analysis.7

Postmenopausal women with HR+/HER2 aBC receiving KISQALI + fulvestrant achieved a 30% reduction in the risk of progressing to chemotherapy vs placebo + fulvestrant (HR 0.70 [95% CI: 0.55–0.88])1

MONALEESA-3: Time to chemotherapy with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal women (ITT analysis; N=726; data cutoff 3 June 2019)1

 

Graph to show time to chemotherapy with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal women over 48 months (ITT analysis; N=726; data cutoff 3 June 2019) for MONALEESA-3.

Adapted from Slamon DJ, et al. 2020.1

Time to chemotherapy was an exploratory endpoint and was defined as the time from randomisation to the beginning of the first chemotherapy after discontinuing study treatment.1

 

In a further exploratory analysis, with a median follow-up  of 56 months, the need for chemotherapy in postmenopausal patients with HR+/HER2 aBC was delayed by up to 4 years with KISQALI + fulvestrant7

MONALEESA-3: Time to chemotherapy with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal women (ITT analysis; N=726; data cutoff 30 October 2020)7

 

Graph to show time to chemotherapy with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal women over 64 months (ITT analysis; N=726; data cutoff 3 June 2019) for MONALEESA-3.

Adapted from Slamon DJ, et al. 2021.7

These results are exploratory in nature; as such, there was no prespecified statistical procedure controlling for type 1 error.

KISQALI + fulvestrant helps you give more time worth having to HR+/HER2 postmenopausal patients with aBC by preserving their quality of life8

In the ITT population (N=726):

Median TTD ≥10% in HRQoL was 35.9 months with KISQALI + fulvestrant (n=159/484) vs 33.1 months with placebo + fulvestrant (n=83/242) (HR 0.81 [95% CI: 0.62–1.06])

 

 

 

 

Time to definitive 10% deterioration (TTD) from baseline in HRQoL (global health status from the EORTC QLQ-C30 questionnaire) and pain (BPI-SF questionnaire) were assessed using Kaplan–Meier estimates.8

Endocrine therapy resistance is a major clinical challenge in patients with ER+ aBC.9

 

KISQALI + fulvestrant, demonstrated longer median overall survival vs placebo + fulvestrant in postmenopausal patients with HR+/HER2 aBC and endocrine-therapy resistance9

In an exploratory analysis of MONALEESA-3, endocrine-resistant patients treated with KISQALI + fulvestrant reached a median OS of 37.5 months vs 31.7 months with placebo + fulvestrant.9

MONALEESA-3: OS with KISQALI + fulvestrant vs placebo +  fulvestrant in postmenopausal patients with HR+/HER2 aBC and endocrine resistance*9

 

Kaplan-Meier graph for MONALEESA-3 showing overall survival over 44 months with KISQALI + fulvestrant vs placebo +  fulvestrant in postmenopausal patients with HR+/HER2- aBC and endocrine resistance.

Adapted from Hurvitz S, et al. 2020.9

These results are exploratory in nature; as such, there was no prespecified statistical procedure controlling for type 1 error.

* The adhoc definition of endocrine resistance in the exploratory analysis of MONALEESA-3 was defined as patients with progressive disease within the first 6 months of first-line endocrine therapy for advanced breast cancer or patients with relapse within the first 2 years of (neo)adjuvant therapy.6,9

The presence of visceral metastases generally signifies a poor prognosis in HR+/HER2- metastatic breast cancer.10

 

KISQALI combined with fulvestrant or an NSAI + LHRH agonist offers longer overall survival in patients with HR+/HER2 aBC and liver metastases vs fulvestrant or NSAI + LHRH agonist alone across two phase III trials10

In MONALEESA-3, postmenopausal women with HR+/HER2− aBC and liver metastases who were treated with KISQALI + fulvestrant achieved an mOS benefit of 36.1 months, vs 24.1 months for those treated with placebo + fulvestrant, reducing their risk of death by 37% (HR 0.629 [95% CI: 0.421–0.942]).10

MONALEESA-3: OS with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal patients with HR+/HER2 aBC and liver metastasis10

 

Kaplan-Meier graph for MONALEESA-3 showing overall survival with KISQALI + fulvestrant vs placebo + fulvestrant in postmenopausal patients with HR+/HER2- aBC and liver metastasis9

Adapted from Yardley DA, et al. 2020.10

27% (197/726) of patients had liver metastases in MONALEESA-3.10

These results are exploratory in nature; as such, there was no prespecified statistical procedure controlling for type 1 error.

1L, first line; 2L, second line; aBC, advanced breast cancer; AI, aromatase inhibitor; ASCO, American Society of Clinical Oncology; BPI-SF, Brief Pain Inventory (short form); CDK4/6i, cyclin-dependent kinase 4 and 6; CI, confidence interval; CNS, central nervous system; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire; ER, endocrine receptor; ET, endocrine therapy;HR, hazard ratio; HR+/HER2−, hormone receptor-positive/human epidermal growth factor 2-negative; HRQoL, health-related quality of life; ITT, intention-to-treat; mOS, median overall survival; mPFS, median progression-free survival; mTTC, median time to chemotherapy; mTTD, median time to deterioration; NICE, National Institute for Health and Care Excellence; NR, not reached; NSAI, non-steroidal aromatase inhibitor; OS, overall survival; PFS, progression-free survival; QoL, quality of life; TTD, time to deterioration.

  1. Slamon DJ, et al. N Engl J Med. 2020;382(6):514–524.
  2. Im S-A, et al. N Engl J Med. 2019;381(4):307–316.
  3. KISQALI (ribociclib). Summary of Product Characteristics.
  4. Slamon DJ, et al. J Clin Oncol. 2018;36(24):2465–2472.
  5. NICE Final Appraisal Document. Ribociclib with fulvestrant for treating hormone receptor-positive, HER2-negative advanced breast cancer after endocrine therapy. Available at: https://www.nice.org.uk/guidance/ta687/documents/final-appraisal-determi.... Accessed June 2021. 
  6. Slamon DJ, et al. N Engl J Med. 2020;382(6):514–524. Supplementary appendix.
  7. Slamon DJ, et al. Presented at ASCO Annual Meeting, 4–8 June 2021.
  8. Fasching P, et al. Breast. 2020;54:148–154. 
  9. Hurvitz S, et al. 329P. Presented at ESMO virtual congress, 19–21 September 2020.
  10. Yardley DA, et al. Poster presented at ASCO20 Virtual Scientific Program, 29–31 May 2020.
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