KEY TAKEAWAYS
- DAWNA-1, a phase 3 trial, tests dalpiciclib and fulvestrant in hormone receptor-positive.
- The trial compares investigator-assessed PFS of dalpiciclib plus fulvestrant vs placebo plus fulvestrant.
- In a double-blind, randomized study, 361 patients were randomly assigned a chance of getting dalpiciclib plus fulvestrant or placebo.
- Compared to placebo plus fulvestrant, dalpiciclib plus fulvestrant significantly prolonged PFS.
- Grade 3 or 4 blood cell count declines were most often neutropenia and leukopenia.
- Pretreated hormone receptor-positive, HER2-negative ABC patients may benefit from dalpiciclib and fulvestrant.
The progression of hormone receptor-positive in advanced breast cancer (ABC) can be slowed by blocking the cyclin-dependent kinase 4 and 6 pathways. The DAWNA-1 (NCT03927456) trial is a phase 3 randomized, double-blind study of dalpiciclib (a novel cyclin-dependent kinase 4 and 6 inhibitors) plus fulvestrant in patients with hormone receptor-positive, HER2-negative ABC whose disease has progressed despite endocrine therapy. 361 patients were split evenly between two treatment groups: dalpiciclib plus fulvestrant and placebo plus fulvestrant.
Investigator-assessed progression-free survival was significantly longer in the dalpiciclib plus fulvestrant group compared to the placebo plus fulvestrant group (median = 15.7 months; 95% CI = 11.1-not reached versus One-sided P < 0.0001 (the border was P ≤ 0.008); hazard ratio = 0.42; 95% CI = 0.31-0.58; median survival time = 7.2 months; 95% CI = 5.6-9.2 months. Neutropenia (84.2%) and leukopenia (62.1%), grade 3 or 4, were the most common adverse events with dalpiciclib plus fulvestrant.
With dalpicilib and fulvestrant, the rate of significant adverse events was 5.8%, while it was 6.7% with placebo and fulvestrant. According to the researcher’s results, dalpiciclib + fulvestrant is an effective novel treatment for patients with hormone receptor-positive and HER2-negative ABC who have previously been treated.
Source: https://pubmed.ncbi.nlm.nih.gov/34737452/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03927456
Xu B, Zhang Q, Zhang P, Hu X, Li W, Tong Z, Sun T, Teng Y, Wu X, Ouyang Q, Yan X, Cheng J, Liu Q, Feng J, Wang X, Yin Y, Shi Y, Pan Y, Wang Y, Xie W, Yan M, Liu Y, Yan P, Wu F, Zhu X, Zou J; DAWNA-1 Study Consortium. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021 Nov;27(11):1904-1909. doi: 10.1038/s41591-021-01562-9. Epub 2021 Nov 4. PMID: 34737452.
