208P - Delayed initiation of HER2-targeted therapy (HER2Tx) is associated with a higher risk of relapse for early stage (ES) HER2-positive (HER2+) breast...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer, Early Stage
Presenter Giuseppe Gullo
Citation Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364
Authors G. Gullo1, R. Bose2, N. Walsh3, M. Maltese1, D. Fennelly4, J. Walshe4, J. Ballot5, J. Crown4
  • 1Medical Oncology, St Vincents University Hospital, 4 - Dublin/IE
  • 2Medical Oncology, St Vincents University Hospital, Dublin/IE
  • 3National Institute For Cellular Biotechnology, Dublin City University, Dublin/IE
  • 4Medical Oncology, St Vincents University Hospital, N/A - Dublin/IE
  • 5Medical Oncology, Cancer Clinical Research Trust, N/A - Dublin/IE

Abstract

Background

The prognosis of HER2+ ESBrCa has improved since the addition of trastuzumab (H) to chemotherapy (CRx). Several H/CRx regimens have been validated in random assignment trials. Some include delayed H, either at the completion of CRx (as per HERA) or, with taxanes (T) after cycles of non-H containing CRx with anthracycline (A) and cyclophosphamide (C) (e.g. AC-TH). Conversely, in the BCIRG TCH program (C = carboplatin), H is administered from day 1.

Methods

We conducted a retrospective analysis of our database of all pts with HER2+ ESBrCa (stages I-III) who received H. The date of first biopsy (Bx) was recorded as the initial diagnosis (Dx). The primary endpoint was relapse-free survival (RFS), i.e. time from start of H to the date of relapse.

Results

We identified 592 pts treated between September 2001 and March 2013 and performed outcome analyses on 452 pts with a minimum of 36 months of follow up (FU). Pts characteristics: Neoadjuvant (NeoA) 95/Adjuvant (Adj) 357, N+ 233 (52%)/N-211 (47%)/unknown = 8 (1%), ER+ 282 (62%)/ER- 167 (37%)/unknown 3. Therapy administered: TCH 251 (56%)/AC-TH 84 (19%)/ other taxane-based + H 37 (8%)/sequential H 13 (3%)/single-agent H/unknown 18 (4%). Median FU is 70.1 months (range 5.5-169.6). The median time from BrCa Dx to first H is 11.9 weeks. Overall RFS rate is 90.5%. The relative risk of relapse for pts starting H > 12 weeks from Dx is significantly increased with an HR 2.55 (95%CI 1.3-4.98 p = 0.006). This effect is particularly evident in pts with ER negative (p = 0.0069), node positive (p = 0.0197), and age

Conclusions

These data suggest the possibility that the timing of initiation of H may be a determinant of outcome. Delay beyond 12 weeks increased the risk of relapse. Intriguingly, the very early administration of H, i.e. pre-operatively completely eliminated the negative prognostic effects of age and nodal status.

Clinical trial identification

Not applicable.

Legal entity responsible for the study

Medical Oncology Department St Vincent's University Hospital

Funding

Medical Oncology Department St Vincent's University Hospital

Disclosure

All authors have declared no conflicts of interest.