Breast Cancer Female
Conditions
Keywords
CDK4/6 inhibitor, ER+, HER2-
Brief summary
POETIC-A is a phase 3 trial which targets post-menopausal primary breast cancer patients with a high 5-year risk of relapse as determined by a high Ki67 after 2 weeks aromatase inhibitor therapy pre-surgery. Eligible patients will be randomised to standard adjuvant endocrine therapy alone or standard adjuvant endocrine therapy with a CDK4/6 inhibitor called abemaciclib.
Detailed description
In women with hormone sensitive early breast cancer, taking a hormone therapy (also known as endocrine therapy) for at least five years after surgery is very effective at reducing the risk of the cancer returning. However, for some women their cancer may eventually become resistant to these drugs. POETIC-A Registration part will identify those who have a higher risk of developing resistance to standard endocrine therapy (ET). At least 8000 women diagnosed with early stage breast cancer will enter the Registration stage from 80 centres. Study doctors will use aromatase inhibitors (AIs), a type of ET, to treat the cancer for between 2 weeks and 6 months before surgery. A sample will be taken from the cancer during surgery and the study laboratory will measure a biological marker called Ki67. If the level of Ki67 does not drop after 2 weeks of AI treatment, the patient is likely to be less sensitive to endocrine therapy, and the study doctor will explore additional treatments after surgery in the POETIC-A Treatment part. Everyone who agrees to join the Treatment stage (2032 patients) will be randomly put into one of the 2 treatment groups; Group1: ET only; or Group2: ET plus a new drug called abemaciclib. The first aim of the Treatment stage is to confirm whether abemaciclib given in combination with ET is more effective than giving ET alone in preventing the cancer coming back. The study laboratory will perform a second test on the cancer sample, called an AIR-CIS test. This test aims to find out if particular groups of patients based on their tumour biology are more suitable for treatment with abemaciclib. Patients in Group 2 will receive ET plus abemaciclib for 2 years. Patients in both groups will have regular study visits during this period.
Interventions
DRUGAbemaciclib
Abemaciclib used in combination with standard Endocrine Therapy for 2 years from randomisation
DRUGEndocrine therapy (letrozole, anastrozole, exemestane or tamoxifen)
Standard of care endocrine therapy for a minimum of 5 years from randomisation
Sponsors
Institute of Cancer Research, United Kingdom
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Registration Stage Inclusion Criteria: 1. Women determined to be postmenopausal according to established local criteria. 2. Diagnosed operable invasive breast cancer with a clinical/radiological tumour size ≥1.0cm\* 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 ASCO/CAP updated guidelines. Patients whose HER2 status is pending/unknown at the time of registration will be allowed to register to 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 stage of the trial and to donation of fresh 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. Registration Stage
Exclusion criteria
1. Men and pre/perimenopausal women. 2. Intended or actual use of HRT or any other oestrogen-containing medication (including vaginal oestrogens) within 4 weeks prior to planned surgery). Note: patient 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 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 1.0cm; 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 or 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 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 stage. (See
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to tumour (local or distant disease) recurrence | from randomisation until tumour recurrence or patient death, assessed up to 5 years | 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 intercurrent deaths will be treated as censoring events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to distant recurrence | from randomisation until distant recurrence or patient death, assessed up to 5 years | the time from randomisation to distant tumour recurrence. Second primary cancers and intercurrent deaths will be treated as censoring events |
| Breast cancer specific survival | from randomisation until patient death from breast cancer, assessed up to 5 years | time from randomisation to death from breast cancer (with or without prior notification of relapse). Intercurrent deaths will be treated as censoring events. |
| Overall survival | from randomisation until patient death, assessed up to 5 years | time from randomisation to death from any cause. |
| Relapse-free-survival | from randomisation until relapse or patient death, assessed up to 5 years | the time from randomisation to local, regional or distant tumour recurrence or death from any cause. |
| Grade 3/4 Adverse Events, SAEs and hospitalisations | from treatment start up to 28 days after treatment discontinuation | assessed by NCI CTCAE v5 |
| Treatment related deaths | 5 years from randomisation | defined as death occurring at any time point after randomisation and assessed to be possibly, probably or definitely related to the intervention |
| Patient reported quality of life | 5 years from randomisation | measured using validated questionnaires which will be defined before the commencement of the relevant sub-study. |
Countries
United Kingdom
Outcome results
None listed