238P - Characterization of circulating tumor cells (CTCs) of metastatic castration resistant prostate cancer (mCRPC) patients in first, second & third lin...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Translational Research
Presenter Howard Scher
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors H.I. Scher1, J. Louw2, R. Krupa2, R.M. Bambury1, D. Danila1, D.E. Rathkopf1, Z. Arslan1, N.A. Schreiber1, A. Jendrisak2, D. Marrinucci2, R. Dittamore2
  • 1Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Translational Research, Epic Sciences Inc., 92121 - San Diego/US

Abstract

Aim

New androgen signaling directed therapies (AR Tx), including abiraterone acetate plus prednisone (AA + P) and enzalutamide (E), prolong survival in patients (pts) with mCRPC. Used sequentially, response to E given after AA + P is of shorter duration and less frequent. Assessing the evolution of the disease to a more resistant phenotype following each treatment is necessary to develop more effective treatment(s). We examined changes in CTC subtypes along with AR expression (exp) and AR localization (LOC) in pts receiving the 1st, 2nd and 3rd+ line of systemic therapy for mCRPC.

Methods

110 blood samples from 88 unique pts (26 with no prior tx, 32 with 1 prior tx, and 52 with 2+ prior tx) were analyzed for CTCs utilizing the Epic Sciences platform and CellSearch®. Epic analysis included identification of four specific CTC subtypes: traditional CTCs (CK + , CD45- cells, intact nuclei, morph distinct), CK- CTCs (CK-, CD45-, intact nuclei, morph distinct), small CTCs (CK + , CD45-, intact nuclei, small cell size), and CTC clusters. CTC AR exp and AR subcellular LOC were evaluated.

Results

CTCs and CTC subtype frequency increased with lines of systemic therapies. Heterogeneity of CTC subtypes, AR exp and LOC also increased.

CTC Events per 7.5mL of Blood
1st line (n = 26) 1st line (n = 26) ≥ 3rd line (n = 52)
Mean PSA (range) 116.0 (0.7 - 1479.8) 170.2 (7.9 - 1516.1) 441.4 (8.5 - 2589.9)
CellSearch® ≥ 5 CellSearch® CTCs 38% 50% 56%
Epic ≥ 5 Traditional CTCs 92% 97% 94%
Epic Mean of All Cell Events (range) 384 (0–4133) 238 (23–2985) 684 (8 - 9705)
% Traditional CTCs 80% 59% 52%
% Non-Traditional CTCs 20% 41% 48%

Conclusions

The frequency of traditional CTCs, CTC Clusters, small CTCs, CK- CTCs, and high nuclear & cytoplasmic AR CTCs increased by line of therapy and increasing disease burden. The increased ratio of non-traditional to traditional CTCs with lines of tx may indicate an evolved, more resistant disease due to increased tx exposure. Increased CTC heterogeneity within and between pts suggests multiple mechanisms of resistance including constitutively active AR signaling, AR signaling independence, and epithelial plasticity. A relationship to disease burden cannot be excluded. This heterogeneity may explain the specific response to new therapies in the post AA + P & E mCRPC.

Disclosure

H.I. Scher: Research funding from Janssen, Janssen Research, and Medivation Uncompensated advisor for Janssen, Janssen Research, and Medivation; J. Louw, R. Krupa, A. Jendrisak, D. Marrinucci and R. Dittamore: I am an employee and stockholder of Epic Sciences. D.E. Rathkopf: Research funding from Janssen, Medivation Uncompensated adviser for Janssen. All other authors have declared no conflicts of interest.