Dalpiciclib (Dalp) plus endocrine therapy (ET) as adjuvant treatment for HR+/HER2– early breast cancer (BC): The randomized, phase 3, DAWNA-A trial.
Year: 2025
Type: conference-abstract
Abstract: 515 Background: Dalp, a potent CDK4/6 inhibitor, has demonstrated significant improvements in PFS when combined with ET in both first-line and later-line settings for HR+/HER2– advanced BC. We conducted a randomized, double-blind, phase 3 trial (DAWNA-A) to further evaluate Dalp with ET as adjuvant therapy for high-risk, early HR+/HER2– BC and here present findings from the pre-specified first interim analysis (IA1). Methods: Women aged 18-75 y, with stage II-III, HR+/HER2– BC, who had completed definitive local therapy (surgery and/or radiotherapy) and had pathologically confirmed ipsilateral axillary lymph node involvement, were enrolled. Patients (pts) were randomized (1:1) to receive oral Dalp (125 mg QD; 3-wk on/1-wk off, for 2 y) + ET (letrozole 2.5 mg/anastrozole 1 mg/tamoxifen 10 mg/toremifene 60 mg QD, for 5 y) or placebo + ET. Pre/peri-menopausal pts received LHRH agonists (perimenopausal use at investigator’s discretion). Stratification factors were menopausal status (pre/peri vs post), clinical stage (II vs III), number of involved nodes (<4 vs ≥4), and adjuvant chemo (y vs n). The primary endpoint was invasive disease-free survival (iDFS). IA1 was pre-planned at ~254 iDFS events (~50% of total expected). As of Oct 25, 2024, 268 iDFS events occurred and IA1 was performed; the actual superiority boundary was a 1-sided p <0.00205 (Lan-DeMets [O’Brien-Fleming] boundary). Results: Between Apr. 30, 2021 and Jul. 19, 2024, 5274 pts were randomized (Dalp, n=2640; placebo, n=2634). As of data cutoff, median follow-up was 20.3 mo (range 0.0–41.9). Dalp + ET significantly prolonged iDFS vs placebo + ET (HR 0.56, 95% CI 0.43–0.71; 1-sided p <0.0001); iDFS benefits with Dalp were generally consistent across stratification factors and other baseline subgroups. DFS and distant DFS (DDFS) also favored Dalp + ET over placebo + ET (Table). TRAEs led to discontinuation of Dalp in 2.1% of treated pts in Dalp arm and of placebo in 0.8% in placebo arm. Tr-SAE occurred in 3.7% and 1.5%, respectively. There was no death due to TRAEs. Conclusions: Addition of Dalp to ET as adjuvant treatment significantly improved iDFS, with a tolerable safety profile. These data support the use of Dalp for treating HR+/HER2- early BC. Clinical trial information: NCT04842617 . Efficacy outcomes. Dalp + ET (n=2640) Placebo + ET (n=2634) iDFS Event, n (%) 98 (3.7) 170 (6.5) 3-y rate * , % (95% CI) 89.1 (85.8–91.7) 86.2 (83.3–88.6) HR † (95% CI); p value ‡ 0.56 (0.43–0.71); p <0.0001 DFS Event, n (%) 108 (4.1) 195 (7.4) 3-y rate * , % (95% CI) 88.0 (84.5–90.7) 83.8 (80.5–86.6) HR † (95% CI); p value ‡ 0.53 (0.42–0.67); p <0.0001 DDFS Event, n (%) 93 (3.5) 149 (5.7) 3-y rate * , % (95% CI) 90.2 (87.2–92.6) 88.7 (86.2–90.8) HR † (95% CI); p value ‡ 0.60 (0.46–0.78); p<0.0001 * Kaplan–Meier method. † Stratified Cox proportional hazards model. ‡ Stratified Log-rank test (1-sided).
Source: Journal of Clinical Oncology
Institutions: Fudan University Shanghai Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Central South University, Jiangsu Province Hospital, Xiangya Hospital Central South University, Third Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Zhengzhou University, Shanxi Provincial Cancer Hospital, Hunan Cancer Hospital, Fourth Hospital of Hebei Medical University, Huazhong University of Science and Technology, Henan Provincial People's Hospital, Zhengzhou University, Henan Cancer Hospital, Union Hospital, Ningxia Medical University, Ningxia Medical University General Hospital, First Affiliated Hospital of Bengbu Medical College, Air Force Medical University, Jiangsu Hengrui Medicine (China)
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Jiangsu Hengrui Medicine
OpenAlex ID: W4410808855