Adding dalpiciclib to treatment with an aromatase inhibitor (AI) improves outcomes in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, according to study findings published in The Lancet Oncology.

Researchers found that dalpiciclib improved responses and progression-free survival (PFS) in the phase 3 DAWNA-2 trial ( identifier: NCT03966898).

The trial included 456 patients with HR-positive, HER2-negative advanced breast cancer. At baseline, the median age was 55 years, 62% of patients were postmenopausal, and 61% had visceral metastases. Thirty-one percent of patients had previously received neoadjuvant or adjuvant endocrine therapy, and 55% had received letrozole or anastrozole.

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Patients were randomly assigned to receive dalpiciclib (n=303) or placebo (n=153), each in combination with letrozole or anastrozole. Patients were treated until disease progression, unacceptable toxicity, consent withdrawal, investigator decision, or study completion. The median follow-up was 21.6 months. 

The median PFS was 30.6 months with dalpiciclib and 18.2 months with placebo (hazard ratio [HR], 0.51; 95% CI, 0.38-0.69; P <.0001). Dalpiciclib improved PFS across most subgroups, including in premenopausal/perimenopausal women (HR, 0.53; 95% CI, 0.33-0.85; P =.0039) and in postmenopausal women (HR, 0.52; 95% CI, 0.36-0.75; P =.0002).

The objective response rate was 57% with dalpiciclib and 48% with placebo (P =.023). There were 2 complete responses in the dalpiciclib arm and no complete responses in the placebo arm. 

The median duration of response was not reached in the dalpiciclib arm and was 15.0 months in the placebo arm. The clinical benefit rate was 87% with dalpiciclib and 80% with placebo (P =.026).

Most patients (90%) in the dalpiciclib arm had grade 3-4 adverse events (AEs), as did 12% of patients in the placebo arm. The most common grade 3-4 AEs in the dalpiciclib arm were neutropenia and leukopenia.

AEs prompted dose reductions in 32% of patients in the dalpiciclib arm and 2% in the placebo arm. The rate of discontinuation due to AEs was 4% and 2%, respectively. In the dalpiciclib arm, there were 2 deaths due to unknown causes that were considered possibly related to the study treatment.

“The findings from this study suggest that dalpiciclib plus letrozole or anastrozole represents a novel standard first-line treatment for patients with hormone receptor-positive, HER2-negative advanced breast cancer, and is an alternative option to the current treatment landscape,” the researchers concluded.

Disclosures: This research was supported by Jiangsu Hengrui Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Zhang P, Zhang Q, Tong Z, et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. Published online May 11, 2023. doi:10.1016/S1470-2045(23)00172-9