Current partner codePEPTIDESDE
NCT07706933·Not applicable·INTERVENTIONAL

Tolerability of Dalpiciclib vs. Abemaciclib/Ribociclib in Early HR+/HER2- Breast Cancer

Status

Not yet recruiting

Phase

Not applicable

Enrollment

456

Locations

0

Results

Not posted

Publications

0

Study summary

What the protocol is testing.

In recent years, the successful application of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has transformed the treatment landscape for HR+/HER2- advanced breast cancer and driven research into their use in adjuvant settings. Large Phase III trials including MONARCH-E and NATALEE have demonstrated that combining CDK4/6i with standard endocrine therapy significantly reduces the risk of recurrence or death in high-risk patients with early breast cancer. This regimen has been recommended by leading domestic and international clinical guidelines. Nevertheless, patients' quality of life, symptom burden and treatment adherence are also critical in clinical practice. Patient-reported outcomes (PROs), especially electronic PROs (ePROs), can effectively complement conventional study endpoints and provide important evidence for the comprehensive evaluation of long-term treatment. This is a prospective, multicenter, randomized controlled clinical trial. The primary objective is to compare the tolerability of dalpiciclib versus abemaciclib/ribociclib, each combined with standard endocrine therapy, in the adjuvant treatment of patients with high-risk HR+/HER2- early breast cancer. Eligible patients who have received curative local therapy will be randomized to either the experimental group (dalpiciclib plus endocrine therapy) or the control group (ribociclib/abemaciclib plus endocrine therapy). Stratified block randomization will be applied, with stratification factors including menopausal status and prior history of neoadjuvant/adjuvant chemotherapy. The total duration of endocrine therapy is 5 years. The treatment duration of CDK4/6i is approximately 104 weeks for dalpiciclib, 156 weeks for ribociclib, and 104 weeks for abemaciclib. CDK4/6i will be discontinued in cases of disease recurrence, intolerable toxicity, patient withdrawal, or discontinuation as determined by the investigator. Patients will be regularly asked to complete ePRO questionnaires throughout the treatment period.

Interventions

Treatment arms and agents.

DRUG

Dalpiciclib

Description: 125 mg orally once daily on days 1-21 of a 28-day cycle (3 weeks on, 1 week off) for 24 months (26 cycles). Receive 5 years of standard endocrine therapy. The recommended treatment drugs are as follows: Letrozole Description: 2.5 mg orally once daily continuously for 5 years as part of standard endocrine therapy. Anastrozole Description: 1 mg orally once daily continuously for 5 years as part of standard endocrine therapy. Tamoxifen Description: 10 mg orally twice daily continuously for 5 years as part of standard endocrine therapy. Toremifene Description: 60 mg orally once daily continuously for 5 years as part of standard endocrine therapy. Premenopausal: Preferred treatment is LHRH agonist plus an aromatase inhibitor. Perimenopausal: LHRH agonist and endocrine therapy may be used per investigator's assessment. Goserelin Description: LHRH agonist administered subcutaneously (e.g., 3.6 mg every 28 days) for ovarian function suppression in premenopausal/perimenopausal

DRUG

Abemaciclib/Ribociclib

Abemaciclib Description: Administered according to approved product labeling. Typical dose: 150 mg twice daily continuously for 24 months. Investigator's choice between abemaciclib and ribociclib. Ribociclib Description: Administered according to approved product labeling. Typical dose: 400 mg orally once daily (3 weeks on, 1 week off) for 36 months. Investigator's choice between abemaciclib and ribociclib. Receive 5 years of standard endocrine therapy. The recommended treatment drugs are as follows: Letrozole Description: 2.5 mg orally once daily continuously for 5 years as part of standard endocrine therapy. Anastrozole Description: 1 mg orally once daily continuously for 5 years as part of standard endocrine therapy. Tamoxifen Description: 10 mg orally twice daily continuously for 5 years as part of standard endocrine therapy. Toremifene Description: 60 mg orally once daily continuously for 5 years as part of standard endocrine therapy. Premenopausal: Preferred treatment is LHRH

Timeline

From registration to results.

  1. First posted

    Jul 16, 2026

  2. Study start

    Aug 1, 2026

  3. Primary completion

    Jun 30, 2028

  4. Study completion

    Jun 30, 2033

  5. Results posted

    Not reported

  6. Registry updated

    Jul 16, 2026

Outcomes

What the study measures.

Primary outcomes

Rate of CDK4/6 inhibitor dose reduction or permanent discontinuation due to any cause by Week 12

Time frame · From randomization up to Week 12 (Day 84, ±7 days)

Rate of CDK4/6 inhibitor dose reduction or permanent discontinuation due to any cause by Week 12

Secondary outcomes

Health-Related Quality of Life - Time to Deterioration (HRQOL-TTD)

Time frame · Up to 5 years (from randomization until deterioration, death, or end of study)

Time from randomization to the first clinically meaningful deterioration (defined as a ≥10-point decrease from baseline) in global health status/quality of life score measured by the EORTC QLQ-C30 (version 3.0). Death before deterioration is handled as a competing risk event.

Change in Functional Domain Scores

Time frame · Baseline to month 24

Change from baseline in physical, role, cognitive, emotional, and social functioning scores measured by the EORTC QLQ-C30 at months 1, 3, 6, 12, 18, and 24. Mixed model for repeated measures (MMRM) will be used to compare trajectories between arms.

. Safety - Incidence and Severity of Adverse Events

Time frame · From signing of informed consent until 28 days after last dose of study drug (up to approximately 5.5 years)

Incidence, severity (graded by NCI-CTCAE version 6.0), and duration of all-grade and grade ≥3 adverse events, serious adverse events (SAEs), adverse events leading to dose modification or treatment discontinuation, and adverse events related to study drugs.

Rate of CDK4/6 Inhibitor Dose Reduction or Permanent Discontinuation by Month 6

Time frame · From randomization up to month 6 (Day 168, ±14 days)

Proportion of participants with a permanent dose reduction or permanent discontinuation of the CDK4/6 inhibitor due to any cause by month 6 (Day 168, window ±14 days), using the same definition as the primary endpoint.

Treatment Adherence - Median Treatment Duration and Relative Dose Intensity

Time frame · From start of treatment to end of CDK4/6 inhibitor treatment period (up to 24 months for dalpiciclib/abemaciclib, up to 36 months for ribociclib)

Median duration of CDK4/6 inhibitor treatment (in months) and relative dose intensity (actual delivered dose / planned dose × 100%) for each treatment arm.

Health Economic Outcome - Quality-Adjusted Life Years (QALYs)

Time frame · From baseline through 5 years of follow-up

Quality-adjusted life years calculated from EQ-5D-5L utility scores using a country-specific value set. Differences in QALYs between arms will be estimated using a generalized linear model, and incremental cost-effectiveness ratios (ICERs) will be calculated.

Invasive Disease-Free Survival (iDFS)

Time frame · From randomization up to 5 years (or until event, censoring, or study completion)

Time from randomization to the first occurrence of any of the following events: invasive ipsilateral or contralateral breast cancer recurrence, local/regional invasive recurrence, distant recurrence, second primary invasive cancer (non-breast), or death from any cause.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: 1. Age ≥18 years with clinical stage II-III breast cancer at the time of signing informed consent. 2. Post-operative pathological confirmation of invasive breast cancer that is hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), as confirmed by the research center's pathology department: * ER positive and/or PR positive defined as ≥10% of tumor cells showing positive nuclear staining. * HER2 negative defined as immunohistochemistry (IHC) 0 or 1+, or negative by in situ hybridization (ISH). 3. Pathologically confirmed unilateral primary invasive breast cancer, with the date of breast cancer diagnosis on the pathology report no more than 18 months before randomization. For patients with multicentric or multifocal tumors, all pathologically examined lesions must meet the pathological requirements in criterion . 4. For patients who received adjuvant chemotherapy: the last chemotherapy dose must be at least 21 days before randomization. 5. For patients who received adjuvant radiotherapy: the last radiotherapy session must be at least 14 days before randomization. 6. The last non-endocrine treatment (including surgery, radiotherapy, chemotherapy) must be within 90 days before randomization. 7. Has undergone curative surgical resection with tumor-free margins on pathological examination, and meets one of the following high-risk categories: * Pathologically confirmed tumor involvement in ≥4 ipsilateral axillary lymph nodes; OR ② Pathologically confirmed tumor involvement in 1-3 ipsilateral axillary lymph nodes AND at least one of the following: a. Pathological primary invasive tumor size ≥5 cm; b. Primary tumor histological grade 3 (G3); c. Ki-67 ≥20%; d. Known genetic test indicating high risk of recurrence. 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 9. No evidence of recurrence or metastatic disease after surgery. 10. Adequate organ and bone marrow function, meeting the following criteria: * White blood cell (WBC) count ≥3,000/mm³ (3.0 × 10⁹/L) (without G-CSF within 14 days); * Absolute neutrophil count (ANC) ≥1,500/mm³ (1.5 × 10⁹/L) (without G-CSF within 14 days); * Platelet count (PLT) ≥100,000/mm³ (100 × 10⁹/L) (without corrective treatment within 7 days); * Hemoglobin (Hb) ≥9 g/dL (90 g/L) (without corrective treatment within 7 days); ⑤ Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥60 mL/min (without corrective treatment within 7 days); ⑥ Total bilirubin (TBIL) ≤1.5 × ULN (without corrective treatment within 7 days); ⑦ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN (without corrective treatment within 7 days); ⑧ QTcF ≤470 ms. 11. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before randomization, and must agree to use acceptable non-hormonal contraception from the signing of informed consent until 7 months after the last dose of dalpiciclib, or 21 days after the last dose of abemaciclib/ribociclib, or 2 months after the last dose of aromatase inhibitor or tamoxifen/toremifene (whichever is longer). 12. All toxicities from prior anti-cancer therapy must have recovered to grade 0-1 (CTCAE version 6.0), except for those explicitly stated in the inclusion/exclusion criteria. 13. Has voluntarily signed the informed consent form, and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: 1. Pathological diagnosis of HER2-positive breast cancer (HER2-positive defined as immunohistochemistry \[IHC\] 3+ or positive by in situ hybridization \[ISH\]). 2. Local or regional recurrence of breast malignancy. 3. Clinical stage IV (metastatic) breast cancer. 4. Bilateral breast cancer (including contralateral carcinoma in situ). 5. History of any malignancy other than breast cancer within 5 years before randomization, excluding adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin. 6. History of severe pulmonary disease such as interstitial pneumonia. 7. Prior treatment with any CDK4/6 inhibitor, other anti-cancer biologic therapy, targeted therapy, or cancer immunotherapy. 8. Concurrent participation in another clinical trial of anti-cancer therapy (including endocrine therapy or immunotherapy). 9. Major surgical procedure, receipt of any investigational drug, other anti-cancer treatment, or use of immunomodulators within 4 weeks before randomization (excluding chemotherapy, radiotherapy, and endocrine therapy for breast cancer). 10. Known infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS); active hepatitis B (HBV DNA ≥500 IU/mL); hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay); or co-infection with hepatitis B and hepatitis C. 11. Any of the following within 6 months before randomization: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class ≥2 heart failure, persistent arrhythmia of grade ≥2 (according to NCI CTCAE version 6.0), atrial fibrillation of any grade, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or pulmonary embolism. 12. Severe infection within 4 weeks before randomization (e.g., requiring intravenous antibiotics, antifungals, or antivirals per clinical practice guidelines), or unexplained fever \>38.5°C during screening or before the first dose. 13. Inability to swallow, intestinal obstruction, or other factors affecting drug administration or absorption. 14. Known hypersensitivity to aromatase inhibitors, tamoxifen-class drugs (e.g., tamoxifen, toremifene), and LHRH agonists; known hypersensitivity to dalpiciclib/abemaciclib/ribociclib or any of their excipients 15. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 16. Known history of substance abuse (including psychoactive drugs). 17. Women within 1 year postpartum or currently breastfeeding. 18. Presence of any other serious physical or psychiatric condition, or laboratory abnormality that may increase the risk of study participation, interfere with study results, or render the patient unsuitable for the study in the opinion of the investigator.

Study locations

0 registered sites.

No country data reported. Showing up to 24 locations stored in the fast local snapshot.

No study locations reported.

Publications

Results and literature.

No PMID-linked publications were present in this registry snapshot.

Primary links

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