1674P - Exploratory study of CK-M30 and pHH3 expression in Circulating Tumor Cells (CTCs) as biomarkers of docetaxel (DOC) efficacy in metastatic castratio...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Prostate Cancer
Genitourinary Cancers
Translational Research
Presenter Paz Nombela Blanco
Citation Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390
Authors P. Nombela Blanco1, R. Lozano Mejorada1, D. Lorente Estelles2, A. Reid3, N. Romero Laorden1, G. Attard3, Y. Cendón Flórez4, J. Mateo5, S. Sandhu6, C. Massard7, A. Montesa8, P. Flohr3, M.I. Sáez9, M.I. Pacheco4, E. Castro Marcos1, J. de Bono10, D. Olmos Hidalgo11
  • 1Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, 28029 - Madrid/ES
  • 2Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia/ES
  • 3Oncology, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 4Prostate Cancer Unit, CNIO- Spanish National Cancer Center, 28029 - Madrid/ES
  • 5Drug Development Unit, The Institute of Cancer Research & Royal Marsden  , Sutton/GB
  • 6Department, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 7Early Drug Development Department, Institut de Gustave Roussy, Villejuif/FR
  • 8Cnio-ibima Genitourinary Research Unit, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga/ES
  • 9Medical Oncology, H Universitario Virgen de la Victoria y Regional de Málaga, Malaga/ES
  • 10Section Of Medicine, Institute of Cancer Research Royal Marsden Hospital, SM2 5PT - Sutton/GB
  • 11Prostate Cancer Clinical Cancer Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid/ES

Abstract

Background

A drop in CTCs counts as early as 4 weeks following treatment initiation have been suggested as an indicator of overall survival (OS) benefit. DOC remains a pivotal treatment in mCRPC for which there are no early pharmacodynamic (PD) markers of its activity in patients (pts). CTCs may be used as surrogate tumor tissue to study PD markers of apoptosis (CK-M30) or mitosis arrest (pHH3) in mCRPC pts receiving DOC.

Methods

We conducted a prospective 2-cohort multicenter exploratory study in mCRPC pts progressing by PCWG2 criteria who were eligible for DOC 75 mg/mˆ2. Pts were prescreened using the CellSearch system and selected if CTCs≥5/7.5mLs of blood (Basal 1). A 2nd blood sample (Basal 2) was drawn in eligible pts within 0-7 days prior to C1D1 of DOC and further samples were collected at 8h, 24h, 7d and 21d. Directly conjugated mAb against pHH3 and CK-M30 were used in combination with CellSearch. Statistical analyses were performed to evaluate the baseline and post-treatment variability. Increases in % of biomarker CTC+ greater than the median baseline variability were correlated with achieving a 50% PSA response (PSA50) and OS from DOC start using chi-square and long-rank test, respectively.

Results

60 mCRPC pts (CK-M30 = 30; pHH3 = 30), 95% ECOG 0-1, 95% and 17% have bone and visceral metastases respectively, received a median of 7 cycles (range 2-10) of DOC. Biomarker results are summarised in Table.Table:

1674P Variability

Basal 1 (N = 60) Median (Range)Basal 2 (N = 57) Median (Range)%marker Corr. CoeffPost-24h (n = 59) median (Range)P-value Basal vs post-24h
Cohort CK-M30CTC/7.5mL9 (5-1266)8 (3-863)0.54 p = 0.7639 (4-1129)NS
CK-M30+48% (0-76%)35% (0-100%)51% (0-100%)
Cohort pHH3CTC/7.5mL10 (5-567)12 (4-623)0.98 p 

Conclusions

pHH3 in CTC+ may be a potential PD biomarker of a favourable response to DOC treatment.

Clinical trial identification

Legal entity responsible for the study

Spanish National Cancer Research Centre

Funding

None

Disclosure

All authors have declared no conflicts of interest.