The POSNOC Study. Amit Goyal MS, MD, FRCS Consultant Oncoplastic Breast Surgeon & Associate Professor Royal Derby Hospital, Derby

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1 The POSNOC Study Amit Goyal MS, MD, FRCS Consultant Oncoplastic Breast Surgeon & Associate Professor Royal Derby Hospital, Derby

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3 Node-negative patients

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6 Node-positive patients

7 Sentinel Node Positive Patients Axillary Node Clearance or Axillary RT? Small tumours Low axillary tumour burden Systemic therapy all node positive <50% will have further nodal disease Local Rx - less likely to influence outcome in poor prognostic tumours

8 Randomized Trial for Patients with Sentinel Node Micrometastasis IBCSG Sentinel Node micrometastasis Randomize ALND No ALND Disease free survival, Overall survival n = 931 BCS - 90%, Mastectomy - 10%

9 IBCSG ALND no ALND Primary endpoint Disease free survival 87.3% 88.4% Secondary endpoint Overall survival 97.6% 98% p=0.48 p=0.35 Median follow-up 57 months

10 NSABP-04 N Engl J Med, 2002; 347:

11 Randomized Trial for Patients with Sentinel Node H&E Metastases ACOSOG Z0011 Sentinel Node Positive Randomize ALND No ALND Breast RT, Systemic Therapy Overall survival, Disease free survival

12 Z0011 ALND SLN only n=420 n=436 ct1 67.9% 70.6% ER+ 83% 83% Macro 62.5% 55.2% Adj. Systemic Rx 96% 97% Axillary recurrence 0.5% (2) 0.9% (4) Median follow-up 6.3 yrs

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14 POSNOC Trial POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy A randomised controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes

15 Hypothesis Treatment of residual disease if any in the axilla does not matter in early stage breast cancer patients receiving systemic adjuvant therapy ULTRASOUND AXILLA

16 Design Randomised, multicentre, non-inferiority trial Sample size Timeline Recruitment 45 months Follow-up 60 months Trial results 120 months (10 years) Pragmatic protocol that closely mimics NHS practice

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18 Outcome measures Primary Axillary recurrence Secondary Arm morbidity (patient reported) Quality of life and anxiety (FACT B+4, STAI) Loco-regional recurrence Distant metastases Axillary recurrence free, disease free and overall survival Economics evaluation

19 Time point Pathway 1 Post-primary surgery registration and randomisation Baseline Verify eligibility Obtain informed consent Registration Intervention/Procedure Pathway 2 Pre-primary surgery registration with intra-operative randomisation Verify eligibility except for sentinel node status, this to be obtained during surgery Informed consent Registration Baseline questionnaires Randomisation 1. Lymphoedema and Breast Cancer Questionnaire and QuickDASH 2. Functional Assessment of Cancer Therapy Breast EQ-5D 4. Spielberger State/Trait Anxiety Inventory Arm 1 no axillary treatment Arm 2 axillary treatment (ANC* or ART ) Intra-operative randomisation following confirmation of eligibility Arm 1 no axillary treatment Arm 2 axillary treatment (ANC* or ART ) Systemic therapy Chemotherapy and/or hormone therapy (endocrine therapy) with or without Herceptin Radiotherapy Breast or chest wall radiotherapy, if indicated. NB: Axillary and SCF radiotherapy is not allowed in Arm 1. Follow-up (months) 3 6# 12# 24# 36** 48# 60** Lymphoedema and Breast Cancer Questionnaire and QuickDASH (arm morbidity) X $$ X $$ X $$ X $$ Functional Assessment of Cancer Therapy Breast +4 and EQ-5D (Quality of life) X $ X $ X $ X $ X $ Spielberger State/Trait Anxiety Inventory (anxiety) X $ X $ X $ X $ X $ Assessment of recurrence or disease progression X X X X X X *ANC = axillary node clearance ART = axillary radiotherapy Where this turns out to be an ineligible patient no further data will be collected # Follow up will be clinic visits (doctor or nurse led) or nurse led telephone follow up ** Follow up will be clinic visits (doctor or nurse led). $ Questionnaires are posted by SHORE-C with up to two reminders. $$ Questionnaires are completed in clinic or over phone.

20 Survey of UK Oncologists Systemic therapy Decisions not influenced by knowledge of status of remaining axillary nodes Radiotherapy Variability in practice Degree of nodal involvement significant driver for the use of post-mastectomy radiotherapy

21 4 or more positive nodes AMAROS 8% in the completion clearance arm

22 Radiotherapy QA Radiotherapy protocol NCRI Radiotherapy Clinical Studies Group Minimum standards have been defined Axillary and SCF radiotherapy not allowed in the Adjuvant therapy alone arm Chest wall radiotherapy allowed as per pre-defined local practice

23 ER-, Grade 3, <50 years Systemic treatment rather than local treatment influences their prognosis Further nodal information not needed to decide adjuvant therapy

24 Funding body HTA NIHR Trial start date Jan 2014 Centres 98

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26 Contact Information Chief Investigator: Amit Goyal, Royal Derby Hospital, Derby Surgeon: Professor Malcolm W Reed, University of Sheffield, Sheffield Clinical Oncologist: Professor David Dodwell, St James Hospital, Leeds Medical Oncologist: Professor Robert Coleman, University of Sheffield, Sheffield Pathologist: Professor Ian Ellis, University of Nottingham, Nottingham Statisticians: Professor Robert Newcombe, Cardiff University, Cardiff; Apostolos Fakis, Royal Derby Hospital, Derby Quality of Life: Professor Lesley Fallowfield and Val Jenkins, University of Sussex, Brighton Health Economist: Professor David Whynes, University of Nottingham, Nottingham Patient Representatives: Independent Cancer Patients Voice