333P - Circulating tumor cell count at baseline is an independent prognostic factor from pathological complete response among patients treated for primary...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Breast Cancer, Locally Advanced
Translational Research
Presenter Jean-Yves Pierga
Citation Annals of Oncology (2014) 25 (suppl_4): iv110-iv115. 10.1093/annonc/mdu328
Authors J. Pierga1, T. Petit2, C. Levy3, J. Ferrero4, M. Campone5, J. Gligorov6, F. Lerebours7, H. Roche8, T. Bachelot9, E. Charafe-Jauffret10, J. Bonneterre11, M. Coudert12, J. Hernandez13, F.C. Bidard1, P. Viens14
  • 1Medical Oncology, Institut Curie, 75248 - Paris CEDEX/FR
  • 2Centre De Lutte Contre Le Cancer, Centre Paul Strauss, FR-67065 - Strasbourg CEDEX/FR
  • 3Sénologie, Centre François BACLESSE, Caen/FR
  • 4Department Of Medical Oncology, Centre Antoine Lacassagne, FR-06189 - Nice CEDEX/FR
  • 5Medical Oncology, Centre René Gauducheau (ICO) Institut de Cancerologie de l'Ouest, 44805 - St Herblain CEDEX/FR
  • 6Oncologie Medicale, APHP, CancerEst, Tenon University Hospital, 75020 - Paris/FR
  • 7Medical Oncology, Institut Curie, FR-92210 - St Cloud/FR
  • 8Oncology Dept, Centre Claudius-Regaud, 31052 - Toulouse CEDEX/FR
  • 9Medical Oncology, Centre Léon Bérard, 69373 - Lyon/FR
  • 10Cancer Center, Institute Paoli Calmettes, 13274 - Marseille CEDEX/FR
  • 11Medical Oncology, Centre Oscar Lambret, FR-59020 - Lille CEDEX/FR
  • 12Biostatistics, Experis IT, Nanterre/FR
  • 13Medical, Roche, Boulogne/FR
  • 14Cancer Center, Institute Paoli Calmettes, 13274 - Marseille CEDEX /FR

Abstract

Aim

The BEVERLY-2 single-arm phase 2 trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast cancer (Pierga JY et al, Lancet Oncol 2012). We report the results of the association between outcome, circulating biomarkers and pathological complete response (pCR) at three years of follow-up.

Methods

Circulating tumor (CTC) and endothelial cell (CEC) counts were assessed at baseline, cycle 5, pre-operative, post-operative and at one year by the CellSearch technique.

Results

52 patients were included. 3-year DFS in patients with ≥1 CTC/7.5 mL at baseline was significantly lower (43% [95% CI: 20; 64]) than for patients with no CTC detected at baseline (81% [95% CI: 62; 91]; hazard ratio 3.69 [1.34; 10.21]; p = 0.012). Due to the low number of CTC-positive patients at all other time points, there was no significant association between CTC and DFS other than that observed at baseline. Detection of CTC at any point during the trial period was associated with a significant reduction in DFS; patients with at least one positive CTC sample had a DFS of 54% (95% CI: 32; 71), compared with a DFS of 83% (95% CI: 61; 93) in patients where no CTC were detected at any time (hazard ratio 3.62 [95% CI: 1.15; 11.39]; p = 0.018). In a multivariate analysis including factors that were associated with DFS in univariate analysis (pCR, SBR grade and baseline CTC status), only SBR grade and baseline CTC status were found to be independent prognostic factors. No impact of CEC count on DFS was observed at univariate analysis. Patients with baseline CTC <1/7.5 mL and a pCR had excellent prognosis (3-year DFS was 95% [95% CI: 71; 99]) while those with baseline CTC ≥1/7.5 mL and no response were at a high risk of relapse (3-year DFS was 38% [95% CI: 9; 67]). At time of analysis, patients with no CTC detected at any time had a 96% OS rate versus 83% for those with at least one CTC value ≥1. The low number of death (n = 5) precluded however any formal statistical comparison.

Conclusions

Combination of pCR and CTC positivity defines specific patient subgroups at very low (no CTC detected at baseline and pCR) and high (CTC detected at baseline and no pCR) risk of early relapse. These parameters could be used to build specific clinical trial with new targeted treatments for patients with inflammatory breast cancer.

Disclosure

J. Pierga: honoraria and research funds from Roche and Janssen diagnotics; M. Coudert: Roche employee; J. Hernandez: Roche employee; P. Viens: Roche research funding. All other authors have declared no conflicts of interest.