A Randomised Trial Comparing Trastuzumab Deruxtecan to CDK4/6 Inhibitors in Non-luminal A, ER-positive/HER2-low Metastatic Breast Cancer
- Conditions
- Metastatic Breast CancerER-positive Breast CancerLuminal BHer2 EnrichedBasal Like
- Interventions
- Registration Number
- NCT06585969
- Lead Sponsor
- Danish Breast Cancer Cooperative Group
- Brief Summary
The objective of this trial, DBCG R25, will be to evaluate the effect of trastuzumab-deruxtecan versus standard of care on progression-free survival (PFS) in first-line for patients with non-Luminal A, ER-positive/HER2-negative metastatic breast cancer
- Detailed Description
Study design and setting We will conduct an international, multicentre, open-label, randomised controlled trial. All oncological departments who treat patients with metastatic breast cancer can participate. The EU Clinical Trial Regulation will be applied.
Interventions Trial participants will be randomised to trastuzumab deruxtecan or standard treatment.
Trastuzumab deruxtecan
Patients randomised to trastuzumab deruxtecan will be treated as:
Trastuzumab deruxtecan until progression or intolerable toxicity, Trastuzumab deruxtecan: 5.4 mg/kg intravenous on day 1 of a 21 days cycle.
Standard
Patients randomised to standard will be treated as:
CDK4/6 inhibitor with an endocrine therapy until progression or intolerable toxicity CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 28 days cycle) or abemaciclib (150mg twice daily).
Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks)
Other treatment Prophylactic antiemetics are allowed, including corticosteroids. Prophylactic antibiotics are allowed if deemed necessary for the patient. G-CSF is allowed when needed.
All other symptomatic treatment to perform best of care is allowed as long as name, administration and length is documented in the chart. Bone targeted agents are allowed. No other antineoplastic treatment is allowed.
Radiological evaluation Patients will initially be scanned every 9-12 weeks as per investigator's or co-investigator's discretion with minimum a CT of the thorax and abdomen or a FDG-PET/CT. Patients with response can have this interval extended. Upon progression treatment/control is to be done according to department preferences, but subsequent treatment and day of death must be registered.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 504
- Women aged 18 or above.
- Radiologically/pathologically verified metastatic breast cancer.
- ER-positive (1% or more) and HER2-low (HER2 1+ or HER2 2+/ISH-neg)10,11.
- PAM50 Luminal B, HER2-enriched or Basal-like.
- Performance status 0-1.
- Evaluable disease
- Patients who are incapable of understanding the written material received
- Patients with inaccessible tumour tissue
- Other malignant disease within 5 years (in situ cervix and non-melanoma skin cancer excluded)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Immunohistochemistry guided treatment (standard) Ribociclib with ET - CDK4/6 inhibitor with an endocrine therapy until progression og intolerable toxicity * CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 4 week schedule) or abemaciclib (125mg twice daily). * Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks) Trastuzumab-deruxtecan Trastuzumab deruxtecan (T-DXd) Trastuzumab deruxtecan until progression or intolerable toxicity: 5.4 mg/kg intravenous on day 1 of a 21 days cycle. Immunohistochemistry guided treatment (standard) Abemaciclib with ET - CDK4/6 inhibitor with an endocrine therapy until progression og intolerable toxicity * CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 4 week schedule) or abemaciclib (125mg twice daily). * Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks)
- Primary Outcome Measures
Name Time Method Primary outcome Up to 4 years after inclusion Progression-free survival (ITT)
- Secondary Outcome Measures
Name Time Method Quality of life During treatment, estimated 18-24 months Quality of life EORTC QLQ-C30/BR23 during treatment and at progression.
Toxicity During treatment, estimated 18-24 months Toxicity on treatment (NCI-CTC v. 5.0)
Overall survival Up to 4 years after inclusion Overall survival in ITT cohort
PFS by subtype Up to 4 years after inclusion PFS by subtype (Luminal B, HER2-enriched and Basal-like)
OS by subtype Up to 4 years after inclusion OS by subtype (Luminal B, HER2-enriched and Basal-like)