Among malignant tumors affecting women, breast cancer consistently ranks first in incidence. Approximately 70% of cases are hormone receptor (HR)–positive and human epidermal growth factor receptor 2 (HER2)–negative. Endocrine therapy is the cornerstone of treatment for this subtype; however, patients with advanced disease frequently develop resistance, leading to a major therapeutic bottleneck.

The introduction of Dalpiciclib (brand name: AiRuiKang®) has helped overcome this challenge. As China’s first independently developed, highly selective CDK4/6 inhibitor, Dalpiciclib offers a new treatment option for patients with HR-positive/HER2-negative breast cancer through its precise mechanism of action, favorable safety profile, and clinical data tailored to Chinese patients. It has reshaped the treatment landscape for this breast cancer subtype.

DengyuePharma provides an overview of Dalpiciclib, covering its drug profile, mechanism of action, indications, and safety.

Drug Profile: A Domestically Developed, Precisely Targeted Antitumor Agent

Dalpiciclib is an orally administered, selective small-molecule antitumor drug independently developed by Hengrui Pharmaceuticals. It is classified as a Category B prescription drug under China’s National Reimbursement Drug List (NRDL). The dosage form is a white film-coated tablet, appearing off-white to pale yellow after removal of the coating. The main active ingredient is dalpiciclib tosylate, with excipients including mannitol and pregelatinized starch. Three strengths are available—50 mg, 125 mg, and 150 mg—allowing flexible dose adjustment according to individual patient needs.

Unlike imported CDK4/6 inhibitors, the entire development of Dalpiciclib focused on the epidemiological and clinical characteristics of Chinese breast cancer patients. All clinical data were derived exclusively from Chinese populations, with 58.9% of patients presenting with visceral metastases and 44% being premenopausal—figures that closely reflect real-world clinical practice in China and provide highly relevant, evidence-based support for treatment decisions.

Since receiving approval from the National Medical Products Administration (NMPA) on December 31, 2021, Dalpiciclib has continued to expand its approved indications. As of May 2025, its application for use as adjuvant therapy in HR-positive breast cancer has been accepted by the NMPA, further broadening the population that may benefit. The drug should be stored in a sealed container at temperatures not exceeding 25°C and has a shelf life of 36 months. It must be used strictly under medical supervision, and patients should not self-medicate or adjust doses without guidance.

Mechanism of Action: Precise Cell-Cycle Blockade to Inhibit Tumor Proliferation

Uncontrolled proliferation of breast cancer cells is closely associated with dysregulation of the cell cycle. Cyclin-dependent kinases 4 and 6 (CDK4/6) are key enzymes regulating the transition from the G1 phase to the S phase and are often overactivated in HR-positive breast cancer, leading to uncontrolled tumor growth and spread. More than half of breast cancer patients overexpress cyclin D, which directly activates CDK4/6, making these kinases critical therapeutic targets.

Dalpiciclib selectively inhibits CDK4/6 activity, preventing their binding with cyclin D and thereby inhibiting downstream phosphorylation of the retinoblastoma (Rb) protein. This arrests tumor cells in the G1 phase, preventing entry into the S phase for DNA replication. As a result, tumor cell proliferation is suppressed and cell-cycle arrest is induced.

Notably, through molecular structure optimization and the introduction of a piperidine moiety, Dalpiciclib eliminates the risk of glutathione trapping, fundamentally reducing potential hepatotoxicity—one of its key advantages over other CDK4/6 inhibitors.

Indications: Covering Advanced and Adjuvant Settings to Benefit More Patients

Based on two pivotal Phase III confirmatory trials (DAWNA-1 and DAWNA-2), Dalpiciclib has been approved in China for two core indications in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer:

1. In combination with an aromatase inhibitor as initial endocrine therapy;

2. In combination with fulvestrant for patients whose disease has progressed following prior endocrine therapy.

In addition, the ongoing DAWNA-A study—a multicenter, randomized, double-blind Phase III trial—has demonstrated that Dalpiciclib combined with endocrine therapy as adjuvant treatment for HR-positive/HER2-negative early or locally advanced breast cancer significantly reduces the risk of recurrence and improves invasive disease-free survival (IDFS). The application for this indication has been accepted, and it is expected to offer a new adjuvant treatment option for early-stage breast cancer, helping to reduce recurrence and improve cure rates.

It should be noted that premenopausal or perimenopausal women receiving Dalpiciclib in combination with endocrine therapy should also receive a gonadotropin-releasing hormone (GnRH) agonist according to standard clinical practice to ensure optimal treatment efficacy.

Safety Profile and Management of Adverse Events

Compared with other CDK4/6 inhibitors, Dalpiciclib demonstrates a more favorable safety profile with more manageable adverse events, making it suitable for long-term use and particularly well aligned with the physical characteristics of Chinese patients. Adverse events are primarily hematologic and largely reversible, while non-hematologic toxicities are generally mild, resulting in good overall tolerability.

Hematologic adverse events are the most common. Decreased neutrophil counts occur in up to 98.5% of patients, with 85.8% experiencing grade ≥3 events. Importantly, no cases of febrile neutropenia were observed in clinical trials. This neutropenia is reversible: unlike chemotherapy-induced myelosuppression, CDK4/6 inhibitors cause cell-cycle arrest rather than apoptosis. Bone marrow cells can rapidly resume proliferation after treatment interruption, with minimal impact on quality of life.

Other common hematologic abnormalities include decreased white blood cell counts (97.9%), anemia (64.9%), and thrombocytopenia (53.8%), though grade ≥3 events are significantly less frequent than neutropenia and can be effectively managed through routine monitoring and dose adjustment.

Among non-hematologic adverse events, rash (24.1%), nausea (17.3%), musculoskeletal pain (17.2%), fatigue (13.9%), oral mucositis (13.5%), and increased serum creatinine (12.0%) are relatively common, but most are grade 1–2. Notably, no grade 3/4 diarrhea was observed, with gastrointestinal adverse events occurring in fewer than 5% of patients, eliminating the need for prophylactic antidiarrheal therapy. Cardiotoxicity risk is extremely low, with QTc prolongation and venous thromboembolism each occurring in less than 1% of patients, making Dalpiciclib suitable for individuals with high cardiovascular risk—another key differentiating advantage.

Adverse event management should follow standardized protocols. During the first 12 months of treatment, complete blood counts are recommended weekly, followed by monthly monitoring once stable. Liver function should be assessed at baseline and monthly thereafter. For grade ≥3 elevations in liver enzymes, treatment should be interrupted and hepatoprotective therapy initiated; treatment may be resumed at a reduced dose once recovery occurs.

For grade 3 neutropenia, treatment should be immediately interrupted and granulocyte colony-stimulating factor (G-CSF) administered. Therapy may be resumed at the same or reduced dose once neutrophil counts recover to ≤ grade 2. For grade 4 or febrile neutropenia, treatment should be withheld until recovery to ≤ grade 2, followed by mandatory dose reduction or, if necessary, discontinuation. Mild adverse events such as rash or fatigue can be managed symptomatically with topical treatments or nutritional support without treatment interruption.

Dalpiciclib is contraindicated in patients with known hypersensitivity to dalpiciclib or any of its components. Patients should inform their physicians of any allergy history, comorbidities, or concomitant medications prior to treatment to avoid potential drug interactions.

Clinical Value and Industry Significance

Clinically, Dalpiciclib has demonstrated outstanding efficacy. In patients with HR-positive/HER2-negative metastatic breast cancer who experienced disease progression after prior endocrine therapy, Dalpiciclib combined with fulvestrant extended median progression-free survival to 15.7 months, reduced the risk of disease progression by 58%, and increased the objective response rate to 27%. These outcomes are significantly superior to endocrine therapy alone, providing patients with prolonged survival and improved quality of life.

In the adjuvant setting, positive results from the DAWNA-A study suggest that more patients with early-stage breast cancer may avoid recurrence and achieve long-term clinical cure.

From an industry perspective, the launch of Dalpiciclib has broken the market monopoly of imported CDK4/6 inhibitors. As an original Chinese innovation, it offers a more cost-effective option and, following inclusion in the NRDL, further reduces patients’ financial burden—allowing broader access to precision targeted therapies. Moreover, the accumulation of China-specific clinical data fills a critical evidence gap for localized CDK4/6 inhibitor use and provides treatment strategies better suited to national clinical realities, advancing China’s breast cancer therapy into an era of “domestic precision medicine.”

Additionally, Dalpiciclib’s lower hepatotoxicity, superior cardiac safety, and absence of severe diarrhea reduce clinical management complexity. With other CDK4/6 inhibitors already included in the reimbursement system, clinicians are well-versed in this drug class, further enhancing accessibility and real-world application for a wider patient population.

Conclusion

As a novel, highly selective CDK4/6 inhibitor independently developed in China, Dalpiciclib Tablets stands out for its precise mechanism of action, strong clinical efficacy, favorable safety profile, and clinical data tailored to Chinese patients. From second-line treatment in advanced disease to adjuvant therapy in early-stage breast cancer, Dalpiciclib continues to expand its therapeutic boundaries, offering personalized treatment options across the disease continuum. It not only prolongs survival but also significantly improves quality of life for patients.

As a benchmark of domestically developed targeted therapy, Dalpiciclib has reduced reliance on imported drugs, lowered treatment costs, and driven independent innovation in China’s breast cancer treatment landscape. With ongoing clinical research, it is expected to play an increasingly important role in breast cancer management—bringing renewed hope to patients and advancing the goal of precision oncology and health protection.