Dalpiciclib Combined with Endocrine Therapy Improves Survival in HR+/HER2- Breast Cancer

Dalpiciclib, in combination with endocrine therapy (ET), has demonstrated a significant enhancement in invasive disease-free survival (iDFS) for patients suffering from hormone receptor-positive (HR+)/HER2-negative breast cancer, according to results from the DAWNA-A trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago. The study indicates that this combination therapy not only improves progression-free survival but also offers a favorable safety profile.

The DAWNA-A trial, a randomized, double-blind phase 3 study, involved 5,274 patients aged between 18 to 75, all diagnosed with stage 2 to 3 HR+/HER2-negative breast cancer with confirmed ipsilateral axillary lymph node involvement. Participants were randomized to receive either dalpiciclib at a dose of 125 mg daily for two years, combined with various forms of ET (including letrozole, anastrozole, tamoxifen, and toremifene), or a placebo combined with ET. The trial's primary endpoint was iDFS, while secondary endpoints included disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and safety assessments.

At the median follow-up of 20.3 months, patients who received dalpiciclib plus ET exhibited a significantly improved iDFS compared to those receiving placebo plus ET, with a hazard ratio (HR) of 0.56 (95% CI 0.43–0.71; 1-sided P < .0001). Importantly, the study found consistent benefits across various subgroups, indicating the robustness of the treatment effect.

Dr. Zhi-Ming Shao, a leading researcher from Fudan University Shanghai Cancer Center, presented the findings, emphasizing, "The phase III DAWNA-A trial met its primary endpoint at the first interim analysis, showcasing significant iDFS benefits with dalpiciclib plus ET versus placebo plus ET." The trial also reported a favorable safety profile, with treatment-related adverse events occurring in only 3.7% of patients in the dalpiciclib arm, compared to 1.5% in the placebo group, underscoring the therapy's tolerability.

Dalpiciclib, an oral cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, works by targeting overexpressed CDK4/6 proteins to disrupt cancer cell proliferation. While it is currently approved in China, in combination with fulvestrant for advanced HR+/HER2-negative breast cancer, it has yet to receive approval from the U.S. Food and Drug Administration (FDA).

These findings are particularly significant given the increasing prevalence of HR+/HER2-negative breast cancer globally. According to the American Cancer Society, this subtype accounts for approximately 70% of all breast cancer diagnoses, making effective treatment options critical. The DAWNA-A trial's results may establish dalpiciclib plus ET as a neoadjuvant treatment option, especially in Chinese populations, where the trial was primarily conducted.

The implications of this trial extend beyond individual patient outcomes, as they contribute to the evolving landscape of breast cancer treatment. The combination therapy offers hope for improved long-term survival rates and a better quality of life for patients grappling with this challenging diagnosis. As research continues, further investigations will be necessary to explore the full potential of dalpiciclib in various treatment settings and its integration into existing therapeutic protocols.

In conclusion, the DAWNA-A trial represents a significant advancement in the management of HR+/HER2-negative breast cancer, with dalpiciclib plus endocrine therapy emerging as a promising option that could redefine treatment standards in both clinical and real-world settings. Continued monitoring of long-term outcomes and safety profiles will be essential as the medical community evaluates this combination therapy's place in breast cancer management.

References: 1. Shao ZM, Hao J, Wang S, et al. Dalpiciclib plus endocrine therapy as adjuvant treatment for HR+/HER2– early breast cancer: The randomized, phase 3, DAWNA-A trial. 2025 ASCO Annual Meeting. Chicago, IL. Abstract 515. 2. Jiangsu Hengrui Medicine Co. (2021). NMPA approves AiRuiKang® (dalpiciclib) for the treatment of relapsed/progressed HR+/HER2- advanced breast cancer. Accessed July 11, 2025. https://www.hengrui.com/en/media/detail-149.html 3. Breastcancer.org. (2022). New CDK4/6 Inhibitor offers benefits for advanced-stage, hormone receptor-positive, HER2-negative breast cancer. Accessed July 11, 2025. https://www.breastcancer.org/research-news/new-cdk46-inhibitor-offers-benefits-for-advanced-stage-hormone-receptor-positive-her2-negative-breast-cancer. 4. ClinicalTrials.gov. (2021). A study of SHR6390 in combination with fulvestrant in patients with HR positive and HER2 negative advanced breast cancer. Updated June 3, 2021. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT03927456.