Efficacy

NATALEE was a randomised, multicentre, open-label, phase III clinical study of KISQALI + AI vs AI alone for the adjuvant treatment of HR+/HER2– EBC. N=5101. Patients received KISQALI 400 mg/day + NSAI for 3 years while NSAI continued ≥5 years. Any (neo)adjuvant ET was permitted for ≤1 year prior to randomisation. Men and premenopausal women also received goserelin. ⁽¹⁾

NATALEE included a wide range of patients with HR+/HER2– EBC. ^(1,2)

Adults wirh anatomic stage II* or III^† (N=5101)

• Any N1, N2, N3
• N0: T2 (G2 + high genomic risk or KI-67 ≥20% or G3), T3, T4

Primary endpoint

• iDFS using STEEP criteria

Secondary endpoint

• Recurrence-free survival
• DDFS
• OS
• HR-QOL
• Safety and tolerability Pharmacokinectics

R1:1

NSAI alone for ≥5 years^‡
(n=2552)

KISQALI 400mg/d for 3 years + NSAI for ≥5 years^‡ (n=2549)

Primary endpoint

• iDFS using STEEP criteria

Secondary endpoint

• Recurrence-free survival
• DDFS
• OS
• HR-QOL
• Safety and tolerability Pharmacokinectics

KISQALI 400mg dose (vs 600 mg in metastatic cancer) selected to help improve tolerability, and potentially, adherence^†

Patients in NATALEE were diagnosed up to 18 months prior to randomisation with HR+/HER2– EBC. Randomisation was stratified by menopausal status, anatomic stage II or III, prior (neo)adjuvant CT and geographic region. Key exclusion criteria: distant metastases of breast cancer beyond the regional lymph nodes and/or evidence of disease after curative surgery; prior treatment with CDK4/6i; prior treatment with anthracyclines at cumulative doses of ≥450 mg/m2 for doxorubicin or ≥900 mg/m2 for epirubicin; major surgery, chemotherapy or radiotherapy within 14 days prior to randomisation; prior treatment with tamoxifen, raloxifene or AIs for reduction in risk of breast cancer and/or prior treatment for osteoporosis in the preceding 2 years. ⁽²⁾

iDFS was defined as the time from randomisation to the date of the first event of local invasive breast cancer recurrence, regional invasive recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin), or death (any cause). ^(1,2)

* Anatomic stage IIA inclusive of N0 (with grade 2 and evidence of high risk: Ki-67 ≥20%, Oncotype DX Breast Recurrence Score ≥26%, or high risk via genomic risk profiling) or grade 3 and N1, and anatomic stage IIB inclusive of N0 or N1. Enrollment of patients with stage II capped at 40%. ^(2)
† Anatomic stage III inclusive of N0, N1, or N3. ^(2)
‡ Men and premenopausal women also received goserelin. ⁽²⁾