Dalpiciclib benefits patients with HR-positive, HER2-negative advanced breast cancer

First results of the DAWNA-1 trial showed increased progression-free survival in patients with HR-positive, HER2-negative advanced breast cancer who relapsed on endocrine therapy and who were treated with dalpiciclib, a new CDK4/6 inhibitor.

For patients with HR-positive, HER2-negative advanced breast cancer, treatment with a CDK4/6 inhibitor combined with endocrine therapy is the standard of care, since it achieves a substantial progression-free benefit, significantly increases overall survival, and either maintains or improves quality of life [1]. Dalpiciclib is a novel CDK4/6 inhibitor that has demonstrated tolerability and preliminary anti-tumour activity in pre-treated HR-positive, HER2-negative advanced breast cancer [2].

DAWNA-1 (NCT03927456) is a randomised, phase 3 clinical trial evaluating the efficacy and safety of dalpiciclib in HR-positive, HER2-negative advanced breast cancer patients who relapsed or progressed on previous endocrine therapy. The trial enrolled 361 patients who were randomised 2:1 to receive dalpiciclib (150 mg once daily, first 3 weeks of every 4 weeks) plus fulvestrant (500 mg, day 1 and 15 of cycle 1, then day 1 every 4 weeks) or placebo plus fulvestrant. The primary endpoint was progression-free survival. Prof. Binghe Xu (Chinese Academy of Medical Sciences and Peking Union Medical College, China) presented the first results of DAWNA-1 [3].

With a median follow-up of 10.5 months, dalpiciclib plus fulvestrant significantly improved median progression-free survival (per independent review committee): 13.6 months versus 7.7 months (HR 0.45; 95% CI 0.32–0.64; P<0.0001; see Figure). Median time to first subsequent chemotherapy was not reached for dalpiciclib versus 14.2 months for placebo.

Figure: Progression-free survival in DAWNA-1 [3]



Grade 3 or 4 toxicity was increased in patients treated with dalpiciclib compared with placebo: 88.3% versus 11.7%. The most common grade 3 or 4 adverse events with dalpiciclib were neutropenia and leukopenia. Treatment discontinuation due to adverse events was reported for 2.5% of patients treated with dalpiciclib versus 3.3% in the placebo arm.

1. 
   
   1. Cardoso F, et al. Ann Oncol. 2020;31:1623-1649.
   2. Zhang P, et al. Biomark Res. 2021;9:24.
   3. Xu B, et al. Dalpiciclib versus placebo plus fulvestrant in HR+/HER2- advanced breast cancer that relapsed or progressed on previous endocrine therapy (DAWNA-1): A multicenter, randomized, phase 3 study. Abstract 1002, ASCO 2021 Virtual Meeting, 4–8 June.

 

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Posted on 12 August 20213 September 2021