[S4-2] Targeted Intraoperative Radiotherapy for Early Breast Cancer: TARGIT-A Trial- Updated Analysis of Local Recurrence and First Analysis of Survival
Vaidya JS, Wenz F, Bulsara M, Joseph D, Tobias JS, Keshtgar M, Flyger H, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sutterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg H, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M. University College London, London, United Kingdom; University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany; University of Notre Dame, Fremantle, Australia; Sir Charles Gairdner Hospital, Perth, Australia; University College Hospital, London, United Kingdom; Royal Free Hospital, London, United Kingdom; University of Copenhagen, Copenhagen, Denmark; Centro di Riferimento Oncologia, Aviano, Italy; University of California, San Francisco, CA; University of Western Australia, Perth, WA, Australia; Red Cross Hospital, Munich, Germany; University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany; Ninewells Hospital, Dundee, United Kingdom; Technical University of Munich, Munich, Germany; University College London Hospitals, London, United Kingdom; National Cancer Research Institute and Independent Cancer Patients' Voice, United Kingdom; Moffit Cancer Centre
Background TARGIT-A, an international phase 3 randomised trial (Lancet 2010;376:91-102) compared outcomes in patients undergoing breast conserving surgery followed by either whole breast external beam radiotherapy (EBRT) over several weeks, or a risk-adaptive approach using single dose targeted intra-operative radiotherapy (TARGIT). Risk-adaptive approach meant that if the final pathology report demonstrated unpredicted pre-specified adverse features, then EBRT was to be added to TARGIT.
Method 3451 women aged 45 years or older with invasive ductal carcinoma were enrolled from 33 centres in 10 countries between 2000 and 2012.
Randomisation to TARGIT or EBRT arm was done either before lumpectomy (pre-pathology) or after lumpectomy (postpathology). If allocated to TARGIT, patients in the pre-pathology group received it immediately after surgical excision under the same anaesthesia; patients in the post-pathology group received it as a subsequent procedure. We pre-specified that analysis would be performed overall as the primary analysis and for these groups separately as a secondary analysis. The primary outcome was ipsilateral within breast recurrence (IBR) with an absolute non-inferiority margin of 2.5% at 5 years and secondary outcome was survival. We performed exploratory analyses for loco-regional recurrence, 'all recurrence' (ipsilateral or contralateral breast, axilla or distant), distant recurrence, and causes of death.
Results 1721 patients were randomly allocated to receive TARGIT and 1730 to EBRT. 1010 patients have a minimum 4 years follow up and 611 patients have minimum 5 years follow up. Primary events have increased from 13 to 34 since 2010.
For the primary outcome of ipsilateral breast recurrence, the absolute difference at 5-years was 2.0%, which was higher with TARGIT and reached the conventional levels of statistical significance (p=0.042), but was within the pre-specified non-inferiority margin; in prepathology the absolute difference in 5-year IBR was 1%; in postpathology it was 3.7%.
For the secondary outcome, there was a non-significant trend for improved overall survival with TARGIT (HR = 0.70(0.46-1.07)) due to fewer non-breast cancer deaths (17 vs. 35, HR 0.47 (0.26-0.84)). Cardiovascular deaths were 1 vs. 10 and deaths from cancers other than breast were 7 vs.16.
|Events||HR (95% CI)|
|5-year cumulative risk (95%CI)|
|Ipsilateral breast recurrenc(IBR)||23||11|
|3.3%(2.1-5.1)||1.3% (0.7-2.5)||2.07 (1.01-4.25)|
|All recurrence (ipsilateral and contralateral breast, axilla and distant)||69||48|