What was the design of the NATALEE trial for KISQALI?

STUDY DESIGN

NATALEE studied the broadest range of patients of any positive CDK4/6 inhibitor trial in stage II/III HR+/HER2- eBC, including all those with node-positive or high-risk node-negative disease 

^aMen and premenopausal women also received goserelin.³

Select exclusion criteria²

• 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

EVENTS INCLUDED IN END POINTS
	PRIMARY	SECONDARY
	iDFS	DDFS
Invasive ipsilateral breast tumor recurrence
Local/regional invasive recurrence
Invasive contralateral breast cancer
Distant recurrence
Death from breast cancer
Death from non–breast cancer 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 eBC²

• 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 safety^1,2

• The once-daily 400-mg starting dose and 3-year duration were studied 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.