Dalpiciclib is a medication used to treat various cancers. It is a targeted therapy that interferes with specific processes in cancer cells to impede their uncontrolled growth. This offers a more precise intervention than traditional therapies, aiming to improve outcomes for patients with certain malignancies.
How Dalpiciclib Works
Dalpiciclib operates by specifically inhibiting cyclin-dependent kinases 4 and 6 (CDK4/6), which are enzymes that orchestrate cell division. These kinases regulate the cell cycle, the process cells undergo to replicate. Their activity is important for the transition from the G1 (growth) phase to the S (DNA replication) phase.
Overactive CDK4 and CDK6, common in cancer cells, promote uncontrolled cell proliferation. Dalpiciclib interferes by preventing phosphorylation of the retinoblastoma (Rb) protein. Unphosphorylated Rb binds to E2F transcription factors, necessary for genes involved in cell division.
By keeping Rb in its active, unphosphorylated state, dalpiciclib halts the cell cycle at the G1 phase. This prevents cancer cells from progressing to DNA replication and division. The targeted nature of this inhibition helps to selectively suppress the growth of tumor cells while minimizing impact on healthy cells.
Therapeutic Applications
Dalpiciclib is primarily used for specific breast cancer subtypes. It is indicated for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. This patient population often has CDK4/6 pathway dysregulation, making them suitable candidates.
It is commonly administered with endocrine therapy. For instance, it is approved with fulvestrant for patients whose cancer progressed after previous endocrine treatment. Clinical trials, such as DAWNA-1, show this combination significantly extends progression-free survival in pre-treated individuals.
Dalpiciclib is also a first-line treatment for HR+/HER2- locally advanced or metastatic breast cancer, often paired with aromatase inhibitors like letrozole or anastrozole. The DAWNA-2 trial demonstrated this combination improved median progression-free survival to 30.6 months compared to 18.2 months with endocrine therapy alone. This benefit was observed across different menopausal statuses, suggesting broad applicability.
Potential Side Effects and Management
Like all medications, dalpiciclib can cause side effects, with some being more common than others. The most frequently reported adverse reactions are hematological, meaning they affect blood cell counts. These include neutropenia, a decrease in a type of white blood cell, and leukopenia, a general reduction in white blood cells.
Other side effects include fatigue, nausea, diarrhea, and abnormal liver enzyme levels. Healthcare professionals monitor patients for these reactions, often through regular blood tests. Neutropenia severity is highest during the initial treatment cycle and may lessen with continued therapy.
Side effect management often involves dose adjustments or supportive care. Patients should communicate any adverse reactions with their healthcare team. This allows for timely intervention and treatment plan adjustments to ensure patient comfort and safety.
Regulatory Status and Patient Access
Dalpiciclib was developed by Jiangsu Hengrui Medicine and approved in China. The National Medical Products Administration (NMPA) of China approved dalpiciclib in December 2021. This approval covers its use with fulvestrant for patients with HR+/HER2- advanced breast cancer that has relapsed or progressed after prior endocrine therapy.
It received Breakthrough Therapy Designation and Priority Review from the NMPA in April 2021, leading to a swift approval process. Dalpiciclib is the first domestically developed CDK4/6 inhibitor approved for marketing in China. Its availability is currently concentrated in this region.
Ongoing research explores additional therapeutic applications, including its use as an adjuvant therapy for early-stage HR+/HER2- breast cancer. Further studies investigate its efficacy and safety when combined with other anti-tumor drugs, aiming to broaden its future clinical utility.