Tolerability of Dalpiciclib vs. Abemaciclib/Ribociclib in Early HR+/HER2- Breast Cancer
ConditionBreast Cancer
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorHenan Cancer Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years with clinical stage II-III breast cancer at the time of signing informed consent.
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).
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 .
Disqualifiers
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.
Pathological diagnosis of HER2-positive breast cancer (HER2-positive defined as immunohistochemistry [IHC] 3+ or positive by in situ hybridization [ISH]).
Local or regional recurrence of breast malignancy.
Clinical stage IV (metastatic) breast cancer.
Trial design
Design model
Parallel
Treatments tested in this trial
Dalpiciclib
DrugDescription: 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
Abemaciclib/Ribociclib
DrugAbemaciclib 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
Treatment groups
456 Participants
are divided into 2 treatment groupsGroup A: Experimental: Dalpiciclib + Standard Endocrine TherapyExperimental treatment 1 intervention
Group B: Control：Abemaciclib/Ribociclib + Standard Endocrine TherapyActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Rate of CDK4/6 inhibitor dose reduction or permanent discontinuation due to any cause by Week 12
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)Secondary outcomes
1
Health-Related Quality of Life - Time to Deterioration (HRQOL-TTD)
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.
Time frame
Up to 5 years (from randomization until deterioration, death, or end of study)2
Change in Functional Domain Scores
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.
Time frame
Baseline to month 243
. Safety - Incidence and Severity of Adverse Events
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.
Time frame
From signing of informed consent until 28 days after last dose of study drug (up to approximately 5.5 years)4
Rate of CDK4/6 Inhibitor Dose Reduction or Permanent Discontinuation by Month 6
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.
Time frame
From randomization up to month 6 (Day 168, ±14 days)Other outcomes
1
Agreement Between Investigator-Reported AEs and Patient-Reported PRO-CTCAE Symptoms
Weighted kappa coefficient for concordance between investigator-graded adverse events (CTCAE) and patient-reported symptom severity/frequency measured by the PRO-CTCAE custom survey for selected symptoms (e.g., nausea, diarrhea, fatigue, joint pain). Detection rate and under-reporting rate will also be calculated.
Time frame
From baseline through end of CDK4/6 inhibitor treatment period (up to 24-36 months)Locations
Sponsors and contacts
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Source ClinicalTrials.gov
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