Trial of Perioperative Endocrine Therapy - Individualising Care (POETIC)

To determine whether perioperative endocrine therapy with an aromatase inhibitor (AI) followed by standard adjuvant therapy improves outcome compared with standard adjuvant therapy alone in postmenopausal women with hormone receptor positive breast cancer.

To determine whether the proliferation marker Ki67 as measured by immunohistochemistry (IHC) in the excised cancer around 2 weeks after starting AI therapy will predict for time to recurrence (TTR) in the individual patient more effectively than the pre-treatment Ki67 value.

To determine whether molecular profiling 2 weeks after starting endocrine therapy predicts for long-term outcome in postmenopausal women with hormone receptor positive breast cancer better than at diagnosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Aromatase Inhibitors

• Study Type: Interventional
• Enrollment (Actual): 4486
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Ashton-Under-Lyne, United Kingdom
    • Tameside General Hospital
  • Bangor, United Kingdom
    • Ysbyty Gwynedd
  • Bath, United Kingdom
    • Royal United Hospital
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Bolton, United Kingdom
    • Royal Bolton Hospital
  • Bournemouth, United Kingdom
    • Royal Bournemouth General Hospital
  • Bristol, United Kingdom
    • Southmead Hospital
  • Bristol, United Kingdom
    • Bristol Royal Infirmary
  • Cambridge, United Kingdom
    • Addenbrooke's Hospital
  • Canterbury, United Kingdom
    • East Kent Hospitals
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • Cottingham, United Kingdom
    • Castle Hill Hospital
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry
  • Crewe, United Kingdom
    • Leighton Hospital
  • Dartford, United Kingdom
    • Darent Valley Hospital
  • Derby, United Kingdom
    • Royal Derby Hospital
  • Exeter, United Kingdom
    • Royal Devon and Exeter Hospital
  • Frimley, United Kingdom
    • Frimley Park Hospital
  • Glasgow, United Kingdom, G11 6NT
    • Western Infirmary
  • Guildford, United Kingdom
    • Royal Surrey County Hospital
  • Hereford, United Kingdom, HR1 2ER
    • Hereford County Hospital
  • Huddersfield, United Kingdom
    • Huddersfield Royal Infirmary
  • Ipswich, United Kingdom
    • Ipswich Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary/ St James' University Hospital
  • Leicester, United Kingdom, LE3 9QP
    • University Hospitals of Leicester NHS Trust
  • Lincoln, United Kingdom
    • Lincoln County Hospital
  • Liverpool, United Kingdom
    • Royal Liverpool University Hospital
  • London, United Kingdom
    • Charing Cross Hospital
  • London, United Kingdom
    • Northwick Park Hospital
  • London, United Kingdom
    • St Bartholomew's Hospital
  • London, United Kingdom, E9 6SR
    • Homerton University Hospital
  • Luton, United Kingdom
    • Luton and Dunstable Hospital
  • Macclesfield, United Kingdom
    • Macclesfield District General Hospital
  • Maidstone, United Kingdom
    • Maidstone Hospital
  • Middlesex, United Kingdom
    • Hillingdon Hospital
  • Milton Keynes, United Kingdom
    • Milton Keynes General Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital
  • Nottingham, United Kingdom
    • Nottingham City Hospital
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Poole, United Kingdom
    • Dorset County Hospital
  • Romford, United Kingdom
    • Queen's Hospital,
  • Salford, United Kingdom, M6 8HD
    • Salford Royal Hospital
  • Salisbury, United Kingdom
    • Salisbury District Hospital
  • Sheffield, United Kingdom
    • Weston Park Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital
  • Stafford, United Kingdom, ST16 3SA
    • Staffordshire General Hospital
  • Stockport, United Kingdom
    • Stepping Hill Hospital
  • Stockton-on-Tees, United Kingdom, TS19 8PE
    • University Hospital of North Tees
  • Taunton, United Kingdom
    • Musgrove Park Hospital
  • Tooting, United Kingdom
    • St George's Hospital,
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay District General Hospital
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital
  • Wakefield, United Kingdom
    • Mid Yorkshire Hospitals
  • Warwick, United Kingdom, CV34 5BW
    • Warwick Hospital
  • Wigan, United Kingdom
    • Royal Albert Edward Infirmary
  • Worthing, United Kingdom
    • Worthing Hospital
  • Belfast
    • Dundonald, Belfast, United Kingdom, BT16 1RH
      • Ulster Hospital
  • Berkshire
    • Slough, Berkshire, United Kingdom, SL2 4HL
      • Heatherwood and Wexham Park Hospitals NHS trust
  • Buckinghamshire
    • Aylesbury, Buckinghamshire, United Kingdom, HP21 8AL
      • Stoke Mandeville Hospital
  • Carmarthenshire
    • Llanelli, Carmarthenshire, United Kingdom, SA14 8QF
      • Prince Philip Hospital
  • Co.Amagh
    • Portadown, Co.Amagh, United Kingdom, BT63 5QQ
      • Craigavon Area Hospital
  • England
    • Ashington, England, United Kingdom, NE63 9JJ
      • Wansbeck General Hospital
    • Barnstaple, England, United Kingdom, EX31 4JB
      • North Devon District Hospital
    • Birmingham, England, United Kingdom, B18 7QH
      • City Hospital - Birmingham
    • Blackburn, England, United Kingdom, BB2 3HH
      • Royal Blackburn Hospital
    • Boston, England, United Kingdom, PE21 9QT
      • Pilgrim Hospital
    • Bradford, England, United Kingdom, BD5 0NA
      • Bradford Teaching Hospitals NHS Trust, St Luke's Hospital
    • Burnley, England, United Kingdom, BB10 2PQ
      • Burnley General Hospital
    • Carlisle, England, United Kingdom, CA2 7HY
      • Cumberland Infirmary
    • Chelmsford, England, United Kingdom, CM2 0QH
      • Chelmsford and Essex Centre
    • Chester, England, United Kingdom, CH2 1UL
      • Countess of Chester Hospital
    • Chesterfield, England, United Kingdom, S44 5BL
      • Chesterfield Royal Hospital
    • Colchester, England, United Kingdom, C03 3NB
      • Essex County Hospital
    • Doncaster, England, United Kingdom, DN2 5LT
      • Doncaster Royal Infirmary
    • Dudley, England, United Kingdom, DY1 2HQ
      • Russells Hall Hospital
    • High Wycombe, England, United Kingdom
      • Wycombe General Hospital
    • Keighley, England, United Kingdom, BD20 6TD
      • Airedale General Hospital
    • Kidderminster, England, United Kingdom, DY11 6RJ
      • Kidderminster Hospital
    • London, England, United Kingdom, NW3 2QG
      • Royal Free Hospital
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden - London
    • London, England, United Kingdom, W2 1NY
      • St. Mary's Hospital
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital
    • London, England, United Kingdom, SE1 9RT
      • Guy's Hospital
    • London, England, United Kingdom, N19 5NF
      • Whittington Hospital
    • Manchester, England, United Kingdom, M23 9LJ
      • Wythenshawe Hospital
    • Manchester, England, United Kingdom, M8 6RB
      • North Manchester General Hospital - Penine Actute Hospitals Trust
    • North Shields, England, United Kingdom, NE29 8NH
      • North Tyneside Hospital
    • Northampton, England, United Kingdom, NN6 8BJ
      • Northampton General Hospital NHS Trust
    • Nuneaton, England, United Kingdom, CV10 7DJ
      • George Eliot Hospital
    • Oldham, England, United Kingdom, OL1 2JH
      • Royal Oldham Hospital
    • Poole Dorset, England, United Kingdom, BH15 2JB
      • Poole Hospital
    • Reading, England, United Kingdom, RG1 5AN
      • Royal Berkshire Hospital
    • Stoke-On-Trent, England, United Kingdom, ST4 7LN
      • University Hospital of North Staffordshire
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden Hosital,
    • Westcliff-On-Sea, England, United Kingdom, SS0 0RY
      • Southend NHS Trust Hospital
    • Winchester, England, United Kingdom, SO22 5DG
      • Royal Hampshire County Hospital
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital
    • Worcester, England, United Kingdom, WR5 1DD
      • Worcester Royal Hospital
    • Yeovil, England, United Kingdom, BA21 4AT
      • Yeovil District Hospital
  • Essex
    • Epping, Essex, United Kingdom, CM16 6TN
      • St Margaret's Hospital
  • Gloucs
    • Gloucester, Gloucs, United Kingdom
      • Cheltenham General Hospital
  • Hertfordshire
    • St Albans, Hertfordshire, United Kingdom, AL3 5PN
      • St Albans City Hospital
    • Welwyn Garden City, Hertfordshire, United Kingdom, AL7 4HQ
      • Queen Elizabeth II Hospital
  • Kent
    • Gillingham, Kent, United Kingdom, ME7 5NY
      • Medway Maritime Hospital
    • Orpington, Kent, United Kingdom, BR6 8ND
      • Princess Royal University Hospital
    • Tunbridge Wells, Kent, United Kingdom, TN2 4QL
      • Tunbridge Wells Hospital
  • Lincolnshire
    • Grantham, Lincolnshire, United Kingdom, NG31 8DG
      • Grantham and District Hospital
  • London
    • Lewisham, London, United Kingdom, SE13 6LH
      • University Hospital, Lewisham
    • Woolwich, London, United Kingdom, SE18 4QH
      • Queen Elizabeth Hospital
  • Middlesex
    • Southall, Middlesex, United Kingdom, UB1 3HW
      • Ealing Hospital
  • Newcastle-Upon-Tyne
    • Newcastle, Newcastle-Upon-Tyne, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary
  • North Yorkshire
    • Harrogate, North Yorkshire, United Kingdom, HG2 7SX
      • Harrogate District Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Belfast City Hospital
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
    • Dumfries, Scotland, United Kingdom, DG1 4AP
      • Dumfries & Galloway Royal Infirmary
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Ninewells Hospital
  • Shropshire
    • Telford, Shropshire, United Kingdom, TF1 6TF
      • Princess Royal Hospital
  • Somerset
    • Weston-Super-Mare, Somerset, United Kingdom, BS23 4TQ
      • Weston General Hospital, Avon
  • South Yorkshire
    • Barnsley, South Yorkshire, United Kingdom, S75 2EP
      • Barnsley District General Hospital
    • Rotherham, South Yorkshire, United Kingdom, S60 2UD
      • Rotherham District General Hospital
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • Ashford and St Peter's Hospitals
    • Kingston Upon Thames, Surrey, United Kingdom, KT2 7QB
      • Kingston Hospital
    • Redhill, Surrey, United Kingdom, RH1 5RH
      • East Surrey Hospital
  • Wales
    • Aberystwyth, Wales, United Kingdom, SY23 1ER
      • Bronglais District General Hospital
    • Haverfordwest, Wales, United Kingdom, SA61 2PZ
      • Withybush General Hospital
    • Rhyl, Wales, United Kingdom, LL18 5UJ
      • North Wales CTC, Glan Clwyd Hospital
    • Swansea, Wales, United Kingdom, SA 2 8QA
      • Singleton Hospital
  • West Glamorgan
    • Port Talbot, West Glamorgan, United Kingdom, SA12 7BX
      • Neath Port Talbot Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Post menopausal women with core biopsy-proven hormone receptor positive invasive breast cancer. Postmenopausal is defined as a woman aged ≥50 years fulfilling any one of the following criteria:

   i) with amenorrhoea >12 months and an intact uterus; ii) has undergone a bilateral oophorectomy; iii) in women who have undergone a hysterectomy, then FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years; or iv) in women who have been on HRT within the last 12 months and therefore not amenorrhoeic, FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years.

2. No evidence of metastatic spread by standard assessment according to local guidelines
3. Standard adjuvant endocrine therapy indicated
4. A palpable tumour of any size , or a tumour with an ultrasound size of at least 1.5cm
5. WHO performance status of 0 or 1
6. Written informed consent to participate in the trial and to donation of tissue (fresh tissue and surplus tissue from diagnostic procedures) and blood samples.

Exclusion Criteria:

1. Locally advanced/inoperable breast cancer
2. Evidence of metastatic disease
3. Previous invasive breast cancer (surgically treated DCIS or LCIS allowed)
4. Current bilateral breast cancer
5. Multiple unilateral tumours with different ER/PgR/HER2 status, grade or type (e.g. ductal vs lobular) i.e. anything that suggests two or more different cancers. Multifocal disease with homogenous ER/PgR/HER2 status, grade and type is allowed if at least one lesion is palpable or at least 1.5cm on ultrasound; the largest lesion should be used for sample collection and CRF completion.
6. Concurrent use (defined as use within 4 weeks prior to diagnostic tissue sample being taken) of HRT or any other oestrogen-containing medication (including vaginal oestrogens)
7. Previous use of oestrogen implants at ANY time
8. Prior endocrine therapy or chemotherapy for breast cancer
9. Any invasive malignancy diagnosed within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ)
10. Any severe co-incident medical disease, inability to give informed consent or unavailability for follow-up
11. Treatment with an unlicensed or investigational drug within 4 weeks before randomisation
12. Current, continuous, long term systemic steroid usage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Aromatase Inhibitor; No aromatase inhibitor given around the time of surgery
Experimental: Aromatase Inhibitor; Aromatase Inhibitor given perioperatively for 4 weeks (two weeks before and two weeks after surgery) Choice of AI is according to centre policy and may be either anastrozole (1mg/day) or letrozole (2.5mg/day)	Drug: Aromatase Inhibitors; Choice of AI is according to centre policy; any brand can be used; Other Names: Letrozole; Anastrazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recurrence	Time to recurrence (TTR) is defined as 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. Patients who are alive and disease free will be censored at the date last seen alive.	5 years post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse free survival	Second primary cancers and deaths from non-breast cancer causes in the absence of breast cancer relapse will be treated as censoring events.	5 years post-randomisation
Time to local recurrence		5 years post-randomisation
Time to distant recurrence		5 years post-randomisation
Overall Survival		5 years post-randomisation
Breast cancer free survival		5 years post-randomisation
Proliferation rate (Ki67)	Comparison of the predictive value of Ki67 at surgery in the perioperative therapy and non perioperative therapy groups will be undertaken using Cox regression, comparing the estimates of the hazard ratios obtained in each treatment group.	At time of surgery (around 2 weeks post-randomisation)
Gene expression profile		At time of surgery (around 2 weeks post-randomisation)

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Investigators: Principal Investigator: Ian Smith, Professor, Royal Marsden NHS Foundation Trust

Publications and helpful links

General Publications

• Smith I, Robertson J, Kilburn L, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Morden J, Sidhu K, Dodson A, Bliss JM, Dowsett M. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1443-1454. doi: 10.1016/S1470-2045(20)30458-7. Erratum In: Lancet Oncol. 2020 Dec;21(12):e553.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2034

Study Registration Dates

• First Submitted: September 16, 2014
• First Submitted That Met QC Criteria: January 9, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Aromatase Inhibitors
• Other Study ID Numbers: ICR-CTSU/2007/10015; 2007-003877-21 (EudraCT Number); CRUK/07/015 (Other Grant/Funding Number: Cancer Research UK); 08/H1102/37 (Other Identifier: Main Research Ethics Committee Number); 63882543 (Registry Identifier: ISRCTN); CCR 2973 (Other Identifier: Sponsor)