Abstract 229P
Background
The randomized, double-blind, phase III DAWNA-1 trial previously showed that the addition of dalpiciclib (SHR6390), a novel cyclin-dependent kinase 4/6 inhibitor, to fulvestrant significantly improved progression-free survival (PFS) in patients with pretreated HR+/HER2− ABC (Nature Medicine 2021). Here we present an updated analysis after >1 year of additional follow-up.
Methods
Patients with HR+/HER2− locally advanced or metastatic BC who had relapsed or progressed after previous endocrine therapy were randomized 2:1 to receive dalpiciclib (150 mg po qd, d1-21, q4w) or placebo with fulvestrant (500 mg im, cycle 1 d1, d15, then d1 q4w). The data cutoff date was Mar. 25, 2022.
Results
The median follow-up was 25.2 mo in the dalpiciclib group (n=241) and 24.5 mo in the placebo group (n=120). Dalpiciclib + fulvestrant prolonged investigator-assessed PFS vs placebo + fulvestrant (median, 16.6 mo [95% CI 15.2-18.6] vs 7.2 mo [95% CI 5.6-9.2]; hazard ratio [HR], 0.50 [95% CI 0.39-0.65]; 1-sided p <0.0001). The PFS benefit with dalpiciclib was consistent in postmenopausal women (HR 0.44 [95% CI 0.31-0.62]) and pre- or perimenopausal women (HR 0.55 [95% CI 0.37-0.82]). 86 (35.7%) patients in the dalpiciclib group and 28 (23.3%) in the placebo group achieved an objective response per investigator; the median duration of response was 20.8 mo (95% CI 17.2-not reached [NR]) and 10.2 mo (95% CI 7.3-21.7), respectively. Benefit beyond initial study treatment was also shown for dalpiciclib over placebo based on time to first subsequent chemotherapy (median, 24.0 mo [95% CI 20.2-NR] vs 11.8 mo [95% CI 9.0-14.5]; HR, 0.61 [95% CI 0.46-0.82]; 1-sided p=0.0005). Overall survival data were not mature with 82 (22.7%) deaths recorded. Treatment discontinuation due to adverse events (AEs) was reported for 2.9% of patients with dalpiciclib + fulvestrant and 4.2% with placebo + fulvestrant; serious AEs were reported for 8.8% and 9.2%, respectively.
Conclusions
The addition of dalpiciclib to fulvestrant continued to demonstrate PFS benefits with no new safety signals identified after prolonged follow-up, further supporting this regimen as a new option for pretreated HR+/HER2− ABC.
Clinical trial identification
NCT03927456.
Editorial acknowledgement
Medical writing support was provided by Xiuzhi Wu, PhD (Jiangsu Hengrui Pharmaceuticals).
Legal entity responsible for the study
Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Funding
Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Disclosure
Z. Tong: Financial Interests, Personal, Research Grant: Jiangsu Hengrui Pharmaceuticals, Novartis, Bio-Thera, Eli Lilly, Company. X. Yan: Financial Interests, Personal, Research Grant: Jiangsu Hengrui Pharmaceuticals. G. Xu, F. Wu, B. Xia: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. B. Xu: Financial Interests, Personal, Advisory Role: Novartis, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Eisai; Financial Interests, Personal, Research Grant: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.