Dalpiciclib plus Fulvestrant in HR-Positive and HER2-Negative Advanced Breast Cancer

Breast cancer is the most often diagnosed cancer in women worldwide and the main cause of cancer-related mortality.¹ Hormone receptor (HR)-positive breast cancer is the most common subtype, accounting for more than 75% of all occurrences.¹ The cornerstone of treatment for HR-positive breast cancer is endocrine therapy; unfortunately, acquired resistance develops in nearly all patients. New treatments that can potentially reverse or at least delay the establishment of hormone resistance are desperately needed.

In the treatment of HR-positive advanced breast cancer, blocking the cyclin-dependent kinase (CDK)4/6 pathway has been proven to be successful.¹ In HR-positive, HER2-negative, advanced breast cancer, several phase 3 trials have evaluated the efficacy of combining a CDK4/6 inhibitor with endocrine therapy.¹ The addition of palbociclib, ribociclib, or abemaciclib to fulvestrant has been shown to improve survival outcomes in patients whose disease has relapsed or progressed on previous endocrine therapy, leading to approval by the US Food and Drug Administration and the European Medicines Agency of these combinations for treating this patient population.¹

Dalpiciclib (SHR 6390) is a novel selective CDK4/6 inhibitor that can be taken orally.¹ It has been shown in preclinical investigations to have significant anticancer efficacy via retinoblastoma protein-dependent cytostasis. The efficacy and safety of dalpiciclib plus fulvestrant in patients with HR-positive, HER2-negative, advanced breast cancer whose disease relapsed or progressed on previous endocrine therapy were assessed in a randomized, double-blind, placebo-controlled phase 3 trial.¹

Serious adverse events were recorded in 5.8% of patients in the dalpiciclib plus fulvestrant group and 6.7% of patients in the placebo plus fulvestrant group.¹ Neutropenia, leukopenia, thrombocytopenia, and lymphopenia were the most prevalent grade 3 or 4 adverse events after dalpiciclib plus fulvestrant treatment.¹

At the interim analysis, dalpiciclib plus fulvestrant significantly improved progression-free survival compared with placebo plus fulvestrant and reduced the risk for disease progression or death by 58% in patients with HR-positive, HER2-negative, advanced breast cancer whose disease had relapsed or progressed on previous endocrine therapy.¹

Reference

1. Xu B, Zhang Q, Zhang P, et al; for the 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;27:1904-1909.