Dalpiciclib Plus Endocrine Therapy in HR+/HER2- Advanced Breast Cancer: DAWNA-2 Trial

On May 11, 2023, Dr. Pin Zhang and colleagues from the Chinese Academy of Medical Sciences published the results of the DAWNA-2 Phase 3 clinical trial in The Lancet Oncology. This study investigated the efficacy and safety of Dalpiciclib, a CDK4/6 inhibitor, in combination with an aromatase inhibitor (Letrozole or Anastrozole) as a first-line treatment for patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer.

Study Design: DAWNA-2 Trial

DAWNA-2 was a multicenter, randomized, double-blind Phase 3 trial. Treatment-naive patients were randomized in a 2:1 ratio to receive:

1. Dalpiciclib Group: Dalpiciclib (150 mg once daily for 3 weeks followed by 1 week off) + Letrozole (2.5 mg) or Anastrozole (1 mg) daily.
2. Placebo Group: Placebo + Letrozole or Anastrozole.

The primary endpoint was progression-free survival (PFS).

Key Efficacy Results (Median Follow-up 21.6 Months)

• Median Progression-Free Survival (PFS):
  • Dalpiciclib Group: 30.6 months
  • Placebo Group: 18.2 months
• The addition of Dalpiciclib resulted in a significant extension of PFS, nearly doubling the time without disease progression compared to endocrine therapy alone.

Safety Profile

The incidence of Grade 3 or 4 adverse events was 90% in the Dalpiciclib group compared to 12% in the placebo group. The most common hematological side effects were:

• Neutropenia: 86% in the Dalpiciclib group vs. 0% in the placebo group.
• Leukopenia: 67% in the Dalpiciclib group vs. 0% in the placebo group.
• Serious Adverse Events: Occurred in 12% of the Dalpiciclib group vs. 7% of the placebo group.

Conclusion

The DAWNA-2 trial demonstrated that the combination of Dalpiciclib and an aromatase inhibitor significantly improves PFS in treatment-naive patients with HR+/HER2- advanced breast cancer. These findings establish Dalpiciclib as a effective new first-line treatment option for this patient population.

Source: The Lancet Oncology - DAWNA-2 Trial Results

#BreastCancer #HRPositive #Dalpiciclib #CDK46Inhibitor #DAWNA2 #CancerResearch #EndocrineTherapy

Figure 1