Source: 2025 ASCO Annual Meeting. May 30 – June 3, 2025. Chicago, IL. Abstract 515.
URL: https://meetings.asco.org/abstracts-presentations/247284
Dalpiciclib plus endocrine therapy significantly improves invasive disease-free survival in high-risk HR-positive/HER2-negative early breast cancer patients, with a 44% reduction in disease recurrence risk. The combination demonstrates manageable toxicity profile with primarily hematologic adverse events, supporting its potential role in adjuvant treatment for this population.
Study Design & Population
- Design: Randomized, double-blind, placebo-controlled phase 3 trial (DAWNA-A)
- Sample: 5,274 patients (2,640 dalpiciclib, 2,634 placebo)
- Population: Stage II-III HR+/HER2- breast cancer with axillary lymph node involvement
- Treatment: Dalpiciclib 125 mg daily (3-weeks-on/1-week-off × 2 years) + standard endocrine therapy × 5 years
- Median follow-up: 20.3 months
Key Findings
- Primary endpoint: 24-month invasive disease-free survival (iDFS) 94.7% vs 90.2% placebo (HR 0.56, 95% CI 0.43-0.71; p<0.0001)
- Secondary endpoints: Disease-free survival (HR 0.53, p<0.0001) and distant disease-free survival (HR 0.60, p<0.0001) both favored dalpiciclib
- Safety: Grade ≥3 adverse events in 84.4% vs 17.3% placebo; discontinuation rates 2.6% vs 1.4%
- Most common toxicities: Neutropenia (97.5%), leukopenia (97.3%), anemia (54.2%)
Clinical Implications
- Establishes dalpiciclib as effective adjuvant CDK4/6 inhibitor for high-risk HR+/HER2- early breast cancer
- Results consistent with other CDK4/6 inhibitors in adjuvant setting, confirming class effect
- Toxicity profile manageable with standard monitoring protocols
- May become treatment option pending regulatory approval outside China
Limitations
- Interim analysis with relatively short median follow-up (20.3 months)
- Overall survival data not yet mature
- Dalpiciclib not currently approved in United States or Europe
- Predominantly Asian population may limit generalizability
- Industry-sponsored trial with potential bias
