The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

A significant improvement in progression-free survival (PFS) was seen with dalpiciclib plus fulvestrant, compared with fulvestrant alone, in patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer in a phase 3 trial.

Binghe Xu, MD, PhD, of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, presented these results at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Dr Xu noted that dalpiciclib (SHR6390) is a CDK4/6 inhibitor that has demonstrated tolerability and preliminary antitumor activity in heavily pretreated HR+, HER2-negative advanced breast cancer.

Continue Reading

Dr Xu reported results of the randomized, phase 3 DAWNA-1 trial ( Identifier: NCT03927456), evaluating the efficacy and safety of dalpiciclib plus fulvestrant in patients with HR+, HER2-negative, metastatic or locally advanced breast cancer that relapsed or progressed on previous endocrine therapy.

The primary endpoint was PFS as assessed by the investigator. As of Nov. 15, 2020, 71.4% of the total projected PFS events had occurred, and a preplanned interim analysis was done.

A total of 361 patients were randomized at a 2:1 ratio to receive dalpiciclib plus fulvestrant (n = 241) or placebo plus fulvestrant (n = 120). At baseline, about 60% of the patients had visceral metastases, and 45% were premenopausal or perimenopausal.

The investigator-assessed PFS was 15.7 months in the dalpiciclib-fulvestrant arm and 7.2 months in the placebo-fulvestrant arm (hazard ratio [HR], 0.42; 95% CI, 0.31-0.58; P <.0001). The median PFS based on an independent review committee (IRC) assessment was 13.6 months and 7.7 months, respectively (HR, 0.45; 95% CI, 0.32-0.64; P <.0001).

The PFS in all prespecified subgroups favored dalpiciclib plus fulvestrant, with a hazard ratio of less than 1 regardless of menopausal status, presence of visceral metastasis, or prior lines of endocrine therapy.

At the time of analysis, the overall survival data were not yet mature.

The investigator-assessed overall response rate (ORR) was 27.0% in the dalpiciclib-fulvestrant group and 20.0% in the placebo-fulvestrant group. The investigator-assessed clinical benefit rate (CBR) was 61.0% and 45.8%, respectively. The IRC-assessed ORR was 30.3% and 15.8%, respectively, and the IRC-assessed CBR was 60.2% and 43.3%, respectively.

The benefit of dalpiciclib versus placebo extended beyond the initial study treatment with time to first subsequent chemotherapy. The risk of initiating first subsequent chemotherapy was reduced by 53% in the dalpiciclib-fulvestrant group compared with the placebo-fulvestrant group (HR, 0.47; 95% CI, 0.32-0.69; P <.0001).

The median duration of exposure was 9.4 months for dalpiciclib and 9.9 months for fulvestrant in the dalpiciclib-fulvestrant group. The median duration of exposure was 6.1 months for fulvestrant in the placebo-fulvestrant group.

The most common adverse events (AEs) in the dalpiciclib-fulvestrant group were grade 3/4 neutropenia (84.2% with dalpiciclib and 0% with placebo) and leukopenia (62.1% and 0%, respectively).

Treatment was discontinued due to AEs in 2.5% of patients in the dalpiciclib arm and 3.3% of those in the placebo arm.

Rates of serious AEs and fatal AEs were low and comparable between the treatment groups. Two patients in the dalpiciclib group (0.8%) and 4 in the placebo group (3.3%) had a fatal AE.

“This phase 3 study met its primary endpoint by demonstrating that dalpiciclib plus fulvestrant significantly improved PFS versus placebo plus fulvestrant,” Dr Xu said. “These findings support dalpiciclib plus fulvestrant as a new treatment option in patients with HR+, HER2-negative advanced breast cancer who relapsed or progressed on endocrine therapy.”

Disclosures: This research was funded by Jiangsu Hengrui Medicine Co., Ltd. Several study authors declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Xu B, Zhang Q, Zhang P, 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. J Clin Oncol. 2021;39:(suppl 15; abstr 1002). doi:10.1200/JCO.2021.39.15_suppl.1002