Dalpiciclib Shows Continued Benefit in Advanced Breast Cancer Treatment

The DAWNA-2 trial, a randomized, double-blind, multicenter phase 3 trial conducted at 42 centers in China, reinforces the efficacy and safety of the CDK4/6 inhibitor dalpiciclib when combined with letrozole or anastrozole as a first-line treatment for hormone receptor (HR)-positive/HER2-negative advanced breast cancer. The interim analysis of DAWNA-2 has been previously published in The Lancet Oncology and demonstrated a statistically significant improvement in progression-free survival (PFS) with the dalpiciclib combination compared with endocrine therapy (ET) alone. At the San Antonio Breast Cancer Symposium, after an additional year of follow-up, the prespecified PFS analysis and updated safety analysis were presented.

DAWNA-2 enrolled 456 patients who were randomly assigned to receive either dalpiciclib plus ET or a placebo plus ET. After a median follow-up of 40.6 months (interquartile range, 30.3-45.1), the results demonstrated that the dalpiciclib combination significantly prolonged investigator-assessed PFS compared with ET alone (median PFS, 33.4 vs 19.3 months; hazard ratio, 95% confidence interval [CI], 0.56 [0.44-0.72]) with no new safety signals. Importantly, this benefit was consistent across different menopausal statuses, indicating that the addition of dalpiciclib is effective for pre- and perimenopausal women and postmenopausal women.

Furthermore, the study found that the dalpiciclib combination resulted in a higher objective response rate compared with the placebo group (59.7% vs 49.7%). This benefit extended to the duration of response (DOR), where the dalpiciclib combination (median DOR; 95% CI, 36.1 [29.4-45.8]) was greater compared with ET alone (median DOR; 95% CI, 16.4 [13.8-24.8]). This suggests that the addition of dalpiciclib not only delays disease progression, but also contributes to a greater likelihood and maintenance of tumor shrinkage.

Beyond the initial treatment phase, dalpiciclib continued to demonstrate benefits. The time to first subsequent chemotherapy was longer in the dalpiciclib group, suggesting that this treatment approach could potentially delay the need for more aggressive therapies. Overall survival data were not available at the time of analysis.

The updated safety analysis, incorporating data from the extended follow-up period, confirms the favorable safety profile of the dalpiciclib combination. The incidence of serious adverse events was low in the dalpiciclib combination (17.5%) and ET alone (7.8%) arms, and few patients discontinued treatment because of adverse events.

These findings solidify the position of dalpiciclib plus letrozole or anastrozole as a valuable first-line treatment option for patients with HR-positive/HER2-negative advanced breast cancer. The significant improvement in PFS, consistent benefit across menopausal groups, and reassuring safety profile highlight the clinical relevance of this combination therapy. The study’s results suggest that the addition of dalpiciclib can not only extend the time patients live without disease progression; it potentially delays the need for subsequent chemotherapy, ultimately contributing to better patient outcomes.

Source

Xu B, et al. Dalpiciclib versus placebo in combination with letrozole or anastrozole as first-line treatment for women with HR+/HER2- advanced breast cancer: prespecified final analysis of progression-free survival of the phase 3 DAWNA-2 trial. Presented at: San Antonio Breast Cancer Symposium. December 10-13, 2024; San Antonio, TX. Abstract SESS-720.