Abemaciclib Dose Escalation in Early High-Risk Breast Cancer Adjuvant Therapy

Official title

Study on the Safety and Efficacy of Abemaciclib Dose Escalation Strategy in Adjuvant Therapy for Early High-Risk Breast Cancer

Overview

Abemaciclib combined with endocrine therapy has become one of the important adjuvant treatment regimens for patients with HR+/HER2- high-risk early breast cancer. However, adverse events such as diarrhea, fatigue, neutropenia and elevated liver enzymes are concentrated in the early stage of adjuvant therapy, which often lead to dose reduction, temporary drug interruption or even permanent discontinuation. This further affects treatment adherence, relative dose intensity (RDI) and treatment completion rate. Findings from the TRADE study suggest that a step-up dosing strategy, initiating at a lower dose followed by gradual titration to the standard dose, combined with standardized patient education and symptomatic management, may improve early treatment tolerance, reduce the burden of partial toxicities, and increase the likelihood of patients achieving and maintaining abemaciclib 150 mg twice daily. Based on the above evidence and clinical experience, step-up dosing has been adopted by some clinicians for real-world clinical practice. Nevertheless, existing evidence is mainly derived from non-Chinese populations. There is still a lack of systematic real-world data on step-up dosing among Chinese breast cancer patients under routine outpatient management, including the early toxicity profile, dose escalation achievement rate at each stage, dose adjustment pathways (prolonged escalation, treatment pause or dose de-escalation), RDI distribution, correlation with quality of life, and baseline factors affecting treatment tolerance and dose target attainment. Therefore, it is necessary to conduct a real-world study focused on Chinese patients to fill the gap in local clinical evidence, and provide a basis for clinical pathway formulation, patient education, and subsequent multicenter validation studies.

Interventions

• Other Dose escalation
  Patients receiving postoperative abemaciclib step-up dosing regimen. Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
• Drug Dose Escalation
  Patients receiving postoperative abemaciclib step-up dosing regimen. Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).

Primary outcome measures

• Rate of inadequate dosing [Time frame: From enrollment to the end of treatment at 12 weeks]

Secondary outcome measures (2)

• Dose Target Attainment and Treatment Intensity [Time frame: From enrollment to the end of treatment at 12 weeks"]
• QoL deterioration rate [Time frame: From enrollment to the end of treatment at 12 weeks.]

Eligibility criteria

Inclusion criteria

• Aged ≥18 years;
• Pathologically confirmed breast cancer with ER and/or PR positive, HER2 negative;
• Completed radical mastectomy/radiacal breast surgery;
• Plan to receive abemaciclib combined endocrine therapy for at least 12 weeks, with abemaciclib administered via a step-up dosing regimen;
• ECOG performance status 0-1;
• Adequate organ function meeting medication requirements (routine blood test, liver and renal function, and other indicators consistent with clinical medication safety criteria);
• Signed written informed consent.

Exclusion criteria

• Previous exposure to any CDK4/6 inhibitor;
• Active infection or severe infection requiring systemic anti-infective treatment;
• Significant gastrointestinal diseases such as chronic diarrhea, inflammatory bowel disease, short bowel syndrome, which may affect drug absorption or increase the risk of diarrhea;
• Significant baseline hepatic or renal dysfunction, or uncontrolled severe comorbidities judged by the investigator to affect safety or treatment adherence;
• Pregnancy or lactation;
• Any other condition deemed ineligible for enrollment by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mayer EL, Trapani D, Kim SE, Faggen M, Sinclair N, Sanz-Altamira P, Battelli C, Berwick S, Lo S, Acevedo J, Sinclair S, Malcolm A, Varella L, Sammons S, Schumer S, Poorvu PD, Wallace E, Pasternak E, Tayob N, Tolaney SM. TRADE: a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer. Ann Oncol. 2026 Jan;37(1):117-124. doi: 10 PMID 41110695
• Goetz MP, Cicin I, Testa L, Tolaney SM, Huober J, Guarneri V, Johnston SRD, Martin M, Rastogi P, Harbeck N, Shahir A, Wei R, Andre V, Rugo HS, O'Shaughnessy J. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study. NPJ Breast Cancer. 2024 Apr 26;10(1):34. doi: 10.1038/s41523-024-00639-1. PMID 38671001
• Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, Campone M, Neven P, Huang CS, Huober J, Jaliffe GG, Cicin I, Tolaney SM, Goetz MP, Rugo HS, Senkus E, Testa L, Del Mastro L, Shimizu C, Wei R, Shahir A, Munoz M, San Antonio B, Andre V, Harbeck N, Martin M; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early brea PMID 36493792
• Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortes J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine The PMID 32954927

Identifiers

NCT: NCT07599137 · BC-P40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗