NATALEE Trial | eBC | KISQALI® (ribociclib)

KISQALI + AI—studied in a uniquely inclusive phase III trial

NATALEE was a positive study of KISQALI efficacy and safety in the broadest range of patients at high risk of recurrence, including those with no nodal involvement.

STUDY DESIGN

NATALEE was a randomized, multicenter, open-label, phase III clinical trial of KISQALI + AI vs AI alone for the adjuvant treatment of HR+/HER2- eBC

Study population in NATALEE (N=5101): pre- and postmenopausal women and men with anatomic stage II or III HR+/HER2- eBC, including high-risk node-negative or node-positive disease (N0: T2 [G2 + high genomic risk or Ki-67 ≥20% or G3], T3, T4; All N1; All N2; All N3). 1:1 randomization. Study treatment was given for 3 years: KISQALI 400 mg/day (3 weeks on/1 week off) with an AI* (n=2549) vs AI alone* (n=2552); the AI was continued for 5 years. The long-term follow-up is up to ~91 months.

*Men and premenopausal women also received goserelin.²

Select exclusion criteria³

Prior treatment with a CDK4/6 inhibitor
ECOG performance status ≥2
Major surgery, chemotherapy, or radiotherapy within 14 days prior to randomization
Treatment with tamoxifen, raloxifene, or AIs for reduction in risk of breast cancer and/or treatment for osteoporosis within the last 2 years

AI, aromatase inhibitor; CDK, cyclin-dependent kinase; eBC, early breast cancer; ECOG, Eastern Cooperative Oncology Group; G, grade; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; N, nodal status; T, tumor size.

END POINTS

Reducing the risk of recurrence—including distant recurrence with incurable metastatic disease—was the primary treatment goal in NATALEE

Invasive disease-free survival (iDFS), the primary end point in NATALEE, includes local and distant recurrence and death, while distant disease-free survival (DDFS) excludes local recurrence^1,5

Table showing events included in iDFS and DDFS endpoints. In iDFS: Invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, invasive contralateral breast cancer. In both iDFS and DDFS: distant recurrence, death from breast cancer, death from non-breast cause, death from unknown cause, second primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin).

iDFS and DDFS were defined as the time from randomization to the date of the first event^1,5
Overall survival (OS) is a secondary end point in NATALEE. At the time of iDFS final analysis, OS data were immature and analysis is ongoing¹
Health-related quality of life (HRQOL) is an additional secondary end point in NATALEE⁵

PRIOR ET & DOSING

The NATALEE trial was designed to help patients start and stay on KISQALI + AI—whether new to adjuvant therapy or already on ET

Patients were eligible for KISQALI even with up to 1 year of prior ET—the most inclusive ET eligibility window of any positive CDK4/6 inhibitor trial in eBC³

NATALEE is the only positive trial of a CDK4/6 inhibitor to allow endocrine-based therapy for up to 1 year prior to randomization, so patients who began ET within the last year may still be candidates for treatment with KISQALI

Dosing was intentionally chosen for the adjuvant setting with the goal of balancing efficacy and safety³

NATALEE studied the 400-mg starting dose and 3-year duration with the goal of minimizing dose-dependent adverse reactions and adherence issues related to tolerability—with the least possible impact on efficacy

ET, endocrine therapy.

PATIENT POPULATION

KISQALI is the only CDK4/6 inhibitor proven and FDA approved for all stage II/III node-positive and high-risk node-negative disease

KISQALI eligibility in stage II/III HR+/HER2- eBC by nodal status. About 50% of patients with stage II/III HR+/HER2- eBC have N0 with high risk features (G3 or T2 G2 with Ki-67 ≥20% or high genomic risk; or T3, T4) or N1 with G1/G2 or tumor size <5 cm—and KISQALI is the only FDA approved CDK4/6 inhibitor for these patients. Additional eligibility includes N1 with G3 or tumor size ≥5 cm, and N2/N3 (all patients). Not eligible: N0 without high-risk features (T2 G1 or G2 without additional risk factors).

High genomic risk may be determined by any of the following test scores²:

Oncotype DX^®: ≥26
Prosigna^® PAM50: High risk
MammaPrint^®: High risk
EndoPredict^®: High risk

Patient populations in the NATALEE and monarchE trials³

Chart with 4 columns: AJCC Anatomic Staging, TN (M0), NATALEE, and monarchE. The NATALEE column has checkmarks in all TNM categories within stage II and stage III, with criteria for T2N0: only if grade 3, or grade 2 with Ki-67 ≥20% or high genomic risk. The monarchE column lists Xs for T2N0 and T4N0, and checkmarks for the remaining TNM categories with criteria for T0N1 (only if grade 3), T1N1 (only if grade 3), T2N1 (only if grade 3), and T4N1 (only if tumor size ≥5 cm or grade 3).

This information is not intended to compare the efficacy or safety outcomes of the clinical trials or their treatments. No implication of superiority or inferiority is intended or should be inferred.

In NATALEE, 0.4% and 0.2% of patients had stage I disease in the KISQALI + NSAI and NSAI-alone arms, respectively. In monarchE, 0.1% of patients in the abemaciclib + ET arm had stage IA disease^2,7
NATALEE allowed ET for ≤1 year prior to randomization; monarchE allowed ET for ≤3 months prior to randomization^2,7

AJCC, American Joint Committee on Cancer; FDA, US Food and Drug Administration; NSAI, nonsteroidal aromatase inhibitor.

NATALEE—a uniquely inclusive phase III trial, so you can identify and treat patients with confidence.

Explore the KISQALI patient profiles

Identify eligible patients like Jasmine, Erin, and Katrice today

DISCOVER NOW

< PREVIOUS: Risk of recurrence

EFFICACY
NEXT: Invasive disease-free survival >

KISQALI + AI—studied in a uniquely inclusive phase III trial

NATALEE was a randomized, multicenter, open-label, phase III clinical trial of KISQALI + AI vs AI alone for the adjuvant treatment of HR+/HER2- eBC

Select exclusion criteria³

Reducing the risk of recurrence—including distant recurrence with incurable metastatic disease—was the primary treatment goal in NATALEE

Invasive disease-free survival (iDFS), the primary end point in NATALEE, includes local and distant recurrence and death, while distant disease-free survival (DDFS) excludes local recurrence^1,5

The NATALEE trial was designed to help patients start and stay on KISQALI + AI—whether new to adjuvant therapy or already on ET

Patients were eligible for KISQALI even with up to 1 year of prior ET—the most inclusive ET eligibility window of any positive CDK4/6 inhibitor trial in eBC³

Dosing was intentionally chosen for the adjuvant setting with the goal of balancing efficacy and safety³

KISQALI is the only CDK4/6 inhibitor proven and FDA approved for all stage II/III node-positive and high-risk node-negative disease

Patient populations in the NATALEE and monarchE trials³

Explore the KISQALI patient profiles

IMPORTANT SAFETY INFORMATION

Indications

KISQALI + AI—studied in a uniquely inclusive phase III trial

NATALEE was a randomized, multicenter, open-label, phase III clinical trial of KISQALI + AI vs AI alone for the adjuvant treatment of HR+/HER2- eBC

Select exclusion criteria3

Reducing the risk of recurrence—including distant recurrence with incurable metastatic disease—was the primary treatment goal in NATALEE

Invasive disease-free survival (iDFS), the primary end point in NATALEE, includes local and distant recurrence and death, while distant disease-free survival (DDFS) excludes local recurrence1,5

The NATALEE trial was designed to help patients start and stay on KISQALI + AI—whether new to adjuvant therapy or already on ET

Patients were eligible for KISQALI even with up to 1 year of prior ET—the most inclusive ET eligibility window of any positive CDK4/6 inhibitor trial in eBC3

Dosing was intentionally chosen for the adjuvant setting with the goal of balancing efficacy and safety3

KISQALI is the only CDK4/6 inhibitor proven and FDA approved for all stage II/III node-positive and high-risk node-negative disease

Patient populations in the NATALEE and monarchE trials3

Explore the KISQALI patient profiles

Select exclusion criteria³

Invasive disease-free survival (iDFS), the primary end point in NATALEE, includes local and distant recurrence and death, while distant disease-free survival (DDFS) excludes local recurrence^1,5

Patients were eligible for KISQALI even with up to 1 year of prior ET—the most inclusive ET eligibility window of any positive CDK4/6 inhibitor trial in eBC³

Dosing was intentionally chosen for the adjuvant setting with the goal of balancing efficacy and safety³

Patient populations in the NATALEE and monarchE trials³