1674P - Exploratory study of CK-M30 and pHH3 expression in Circulating Tumor Cells (CTCs) as biomarkers of docetaxel (DOC) efficacy in metastatic castration resistant prostate cancer (mCRPC)

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/m^2. 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.Table1674P VariabilityBasal 1 (N = 60) Median (Range)Basal 2 (N = 57) Median (Range)%marker Corr. CoeffPost-24h (n = 59) median (Range)P-value Basal vs post-24hCohort CK-M30CTC/7.5mL9 (5-1266)8 (3-863)0.54 p = 0.7639 (4-1129)NSCK-M30+48% (0-76%)35% (0-100%)51% (0-100%)Cohort pHH3CTC/7.5mL10 (5-567)12 (4-623)0.98 p < 0.0019 (3-584)<0.001pHH3+0% (0-10%)0% (0-8%)7% (0-67%)ResponseNPSA50p-valueOS median (CI95%)p-valueCK-M30+ change 24hCKM30 + >50%52NS24 m (–)NSCKM30 + <50%251121 m (12-30)pHH3+ change 24hpHH3 + >10%1380.04717 m (12-22)NSpHH3 + <10%16412 m (6-18) Open table in a new tab Conclusions: pHH3 in CTC+ may be a potential PD biomarker of a favourable response to DOC treatment. Legal entity responsible for the study: Spanish National Cancer Research Centre Funding: None Disclosure: All authors have declared no conflicts of interest.