A trial of hormone therapy and abemaciclib for early breast cancer
- Conditions
- Operable invasive breast cancer which is ER positive and HER2 negative, with high (20%) 5-year risk of relapse with endocrine therapy (ET) alone in postmenopausal womenCancerMalignant neoplasm of breast
- Registration Number
- ISRCTN89539429
- Lead Sponsor
- Institute of Cancer Research
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Female
- Target Recruitment
- 2032
Current inclusion criteria as of 12/01/2024:
Registration:
1. Women determined to be postmenopausal according to established local criteria
2. Diagnosed with operable invasive breast cancer with a clinical/radiological tumour size =1.0 cm.
3. Grade 2 or 3 tumours.
4. Preoperative full assessment completed (including bilateral breast examination and imaging with mammogram +/- ultrasound/MRI as performed locally)
5. Tumour ER-positive. ER positivity is defined as =1% cells staining positive (or equivalent Allred Score of ER =3 out of 8)
6. Tumour HER2 negative or HER2 status unknown. HER2 negativity will be defined as per the 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) updated guidelines. Patients whose HER2 status is pending/unknown at the time of
registration will be allowed to register for the trial. However, please note that only patients who are confirmed to be HER2 negative will be eligible to join the randomised part.
7. Received or planned to receive 10 days to 6 months of anastrozole or letrozole prior to surgery
8. Written informed consent to enter the registration part of the trial and to the donation of tissue
9. The patient has given written informed consent prior to any study-specific procedures and is willing and able to make herself available for the duration of the study and amenable and able to follow study schedule during treatment and follow-up and for the use of routinely collected electronic health and related records
Randomisation:
1. Patient previously consented and registered for screening component of POETIC-A
2. Tumour HER2 negative. HER2 negativity will be defined as per the 2018 ASCO/CAP updated guidelines
3. Centrally confirmed Ki67 =8% following pre-surgical AI
4. Patient is expected by the time of treatment initiation to have undergone definitive surgery for the primary breast tumour with clear radial margins as judged by the multidisciplinary team, and will have completed any adjuvant chemotherapy or radiotherapy (if prescribed)
5. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
6. The patient is randomised in time for treatment to start no later than 3 months after completion of non-endocrine therapy (defined as the final fraction of radiotherapy, Day 1 of the final cycle of chemotherapy or the date of the final surgical procedure)
7. The patient is able to swallow oral medications (excluding transient side effects from adjuvant non-endocrine treatment, if randomised before the end of this treatment)
8. The patient intends to take adjuvant endocrine therapy for at least 5 years
9. The patient has given written informed consent prior to any study-specific procedures (for the randomised intervention part), is willing to donate tissue from diagnostic biopsy, and is willing and able to make herself available for the duration of the study and to follow the study schedule during treatment and follow-up and for the use of routinely collected electronic health and related records
Week 1 Day 1:
1. Patient must have undergone definitive surgery for the primary breast tumour with clear radial margins as judged by the multidisciplinary team.
2. Adjuvant chemotherapy, if prescribed, must have been completed prior to Week 1 Day 1, and patients must have recovered (Common Terminology Criteria for Adverse Events, version 5 [CTCAE v5] Grade =1) from the acute effects of chemotherapy except for residual al
Current exclusion criteria as of 12/01/2024:
Registration:
1. Men and pre-/peri-menopausal women
2. Intended or actual use of HRT or any other oestrogen-containing medication (including vaginal oestrogens) within 4 weeks prior to planned surgery (date when surgical tissue sample being taken). Note: patients with a Mirena coil in situ at the time of registration are not excluded.
3. Patients who commenced pre-surgical AI therapy >6 months prior to surgery
4. Prior endocrine therapy for breast cancer or breast cancer prevention
5. Prior neoadjuvant chemotherapy for breast cancer
6. Evidence of metastatic disease
7. Locally advanced breast cancer not amenable to surgery
8. Bilateral invasive breast cancer (excluding contralateral ductal or lobular carcinoma in situ [DCIS/LCIS])
9. Multiple unilateral tumours with different ER and/or HER2 status. Synchronous DCIS/LCIS, as well as multifocal disease with homogenous ER/HER2 status, is allowed if at least one lesion is at least 1.0 cm; the largest lesion should be used for sample collection and CRF completion. If ER/HER2 status of smaller foci is unknown at time of registration, patients can be registered; however, note that congruity of receptor status will need to be confirmed by the time of randomisation (unless smaller foci are <10mm and receptor status is unknown).
10. Previous invasive breast cancer except for ipsilateral DCIS/LCIS treated >5 years previously by locoregional therapy alone or contralateral DCIS/LCIS treated by locoregional therapy at any time
11. Any invasive malignancy diagnosed within the previous 5 years (other than non-melanoma skin cancer or cervical carcinoma in situ)
12. Any other medical condition likely to exclude the patient from subsequent randomisation part (see Randomisation)
Randomisation:
1. Patient has received prior CDK4/6 inhibitor therapy
2. Patient is planned to receive adjuvant abemaciclib as standard of care.
3. Any patient with a history of VTE (for example, DVT of the leg or arm and/or PE) will be excluded. Note: patients with a history of venous catheter occlusion by thrombus that did NOT surround the catheter, and the lumen could be made patent by appropriate measures (for example, saline or thrombolytic agent), are not excluded
4. The patient has a serious/or uncontrolled pre-existing medical condition(s) that, in the judgment of the investigator, is likely to preclude study treatment (such as severe renal impairment, [for example, estimated creatinine clearance <30 ml/min], interstitial lung disease, severe dyspnoea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn’s disease or ulcerative colitis or a pre-existing chronic condition resulting in baseline Grade 2 diarrhoea)
5. The patient has a personal history of any of the following conditions: syncope of cardiovascular aetiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Note: patients with controlled atrial fibrillation diagnosed more than 30 days prior to randomisation are not excluded
6. The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomisation, or is currently enrolled in any other type of medical research (for example: medical device) judged by the Chief Investigator not to be scientifically or
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time to tumour (local or distant disease) recurrence, defined as the time from randomisation to local, regional or distant tumour recurrence or death from breast cancer without prior notification of relapse. Second primary cancers and inter-current deaths will be treated as censoring events. Ongoing follow up through routine data sources via electronic data linkage (from the patients’ national medical records) annually until the end of the study.
- Secondary Outcome Measures
Name Time Method