Abstract Background Adjuvant dalpiciclib (Dalp), a CDK4/6 inhibitor, combined with endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) in patients with HR+/HER2- early breast cancer (EBC) in the first interim analysis of the randomized, double-blind, phase 3 DAWNA-A trial (NCT04842617). We now present updated findings from the prespecified second interim analysis (IA2) after additional follow-up. Methods Women aged 18-75 yrs, with HR+/HER2-, node-positive, stage II-III BC were randomized (1:1) to receive Dalp (125 mg QD, 3-wk on/1-wk off, for 2 yrs) or placebo, both with ET (letrozole 2.5 mg, anastrozole 1 mg, or toremifene 60 mg QD, or tamoxifen 10 mg BID, for ≥5 yrs). Premenopausal (mandatory) and perimenopausal (per investigator) patients also received luteinizing hormone-releasing hormone agonists. Stratification factors were menopausal status (pre/peri vs post), clinical stage (II vs III), number of involved nodes (4 vs ≥4), and adjuvant chemotherapy (yes vs no). The primary endpoint was IDFS. As of Jun. 30, 2025, 378 IDFS events had occurred and the preplanned IA2 was performed. 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 27.0 mo; 70.4% of patients in the Dalp group and 72.1% in the placebo group had completed or discontinued Dalp or placebo. The IDFS benefit with Dalp + ET vs placebo + ET was maintained (HR, 0.60 95% CI 0.49-0.74; nominal 1-sided p 0.0001). The 3-yr IDFS rate was 90.6% with Dalp + ET vs 87.4% with placebo + ET, yielding an absolute difference of 3.2%. Improvement in IDFS with Dalp was consistent across randomization stratification factors and other baseline charactersitics. DFS and distant DFS (DDFS) were also prolonged with Dalp + ET (Table 1). No new safety concerns were identified. Discontinuation of Dalp/placebo due to TRAEs were observed in 2.5% of patients in the Dalp group and 1.0% in the placebo group. No treatment-related deaths occurred. Conclusions Addition of Dalp to adjuvant ET contiuned to show clinically meaningful improvement in IDFS within and beyond the 2-yr treatment period, with a manageable safety profile. These findings support the adjuvant use of Dalp for HR+/HER2- EBC. Citation Format: Z. Shao, J. Hao, S. Wang, Q. Zhang, Y. Gu, F. Tian, S. Wang, Q. Ouyang, L. Zhang, Y. Liu, J. Cheng, S. Cang, Z. Liu, C. Xu, J. Nie, Y. Lv, J. Qian, T. Wang, M. Yu, Y. Pan, Y. He. Dalpiciclib plus endocrine therapy as adjuvant treatment for HR+/HER2- early breast cancer: updated results from the phase 3, DAWNA-A trial abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-13-09.
Shao et al. (Tue,) studied this question.