# Efficacy and Safety of Dalpiciclib in HR-Positive Advanced Breast Cancer: A Two-Center Retrospective Study

## TL;DR

A study of 76 patients found that dalpiciclib, when used early in treatment, improves survival in hormone receptor-positive advanced breast cancer.

## Contribution

This study provides real-world evidence on the efficacy and safety of dalpiciclib in HR+ advanced breast cancer, emphasizing the impact of treatment timing.

## Key findings

- Dalpiciclib combined with endocrine therapy achieved a median progression-free survival of 12 months.
- First-line use of dalpiciclib resulted in significantly better outcomes (17 months) compared to later-line therapy.
- Hematologic toxicities were common but manageable, with no febrile neutropenia reported.

## Abstract

This real-world study evaluated the efficacy and safety of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), in 76 patients with hormone receptor-positive advanced breast cancer. Our findings demonstrate that dalpiciclib combined with endocrine therapy achieves a median progression-free survival of 12 months, with significantly better outcomes when used as first-line treatment (17 months) compared to later-line therapy (10 months for second-line, 4 months for third-line or later). Multivariate analysis identified the treatment line of dalpiciclib and prior chemotherapy as independent predictors of survival outcomes. The safety profile was manageable, with hematologic toxicities being most common but rarely leading to treatment discontinuation. These real-world results suggest that dalpiciclib is an effective treatment option, particularly when introduced early in the treatment course, and highlight the importance of considering treatment sequencing in clinical decision-making.

Background: This study aims to evaluate the real-world efficacy and safety of dalpiciclib in patients with hormone receptor-positive (HR+) advanced breast cancer and explore the impact of different clinical characteristics on treatment outcomes. Methods: This was a two-center, retrospective cohort study involving 76 patients treated with dalpiciclib between January 2022 and June 2024 at two affiliated hospitals of Anhui Medical University in China. Data on progression-free survival (PFS), adverse events, and key clinical factors were collected and analyzed. Kaplan–Meier estimates were used for statistical analysis. Results: The median PFS (mPFS) for the entire cohort was 12.00 months (95% CI: 10.09–13.91 months). Patients receiving dalpiciclib as first-line therapy had significantly better outcomes (mPFS: 17.00 months, 95% CI: 9.19–24.81 months) than those receiving later-line therapy (p < 0.001). Patients with prior exposure to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and those with endocrine resistance had poorer outcomes. Multivariate Cox proportional hazards regression analysis confirmed that earlier treatment line (HR for second-line vs. first-line: 3.89, p = 0.015; HR for third-line or later vs. first-line: 5.56, p = 0.006) and prior CDK4/6i treatment (HR = 3.42, p = 0.040) were independent predictors of PFS. The most common adverse events were hematologic toxicities, including leukopenia (76.6%) and neutropenia (72.4%), mostly grade 1–2. No febrile neutropenia cases were reported, indicating a manageable safety profile. Conclusions: Dalpiciclib combined with endocrine therapy is associated with favorable efficacy and safety in real-world settings, with early-line treatment and lower tumor proliferative activity associated with better outcomes. While findings suggest potential for clinical application, further large-scale prospective studies are needed to validate its effectiveness in different patient subgroups and optimize treatment strategies.