Abstract 675P
Background
Although the role of HER2 in prostate cancer remains controversial, HER2 protein can be overexpressed during prostate cancer progression, and HER2-dependent signaling may support the development of metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling through androgen ligand–independent mechanisms.
Methods
From 41 mCRPC patients (including 31 patients treated with Androgen Receptor Signaling [ARS] inhibitors), Circulating Tumor Cells (CTCs) were prospectively enriched with AdnaTest platform and analyzed with a highly sensitive assay (AdnaPanel platform) for HER2 expression and others biomarkers including AR-V7. Then, we evaluated the impact of HER2 expression on PSA-response and long-term clinical outcomes (PSA-PFS, radiological-PFS and OS). Per-patient analyses for evaluating correlation of HER2 expression between CTCs and soft-tissue metastases are ongoing.
Results
HER2 expression was detected in 26 of 41 patients (63%). Although PSA response was similar regardless of HER2 status, HER2+ patients had shorter PSA-PFS (median of 6.2 months versus 13.0 months, p=0.034) and radiological-PFS (median of 6.8 months versus 25.6 months, p=0.022) compared to HER2- patients. HER2 expression was also associated with a non-significant trend for shorter OS (median 22.7 months versus not reached, p=0.05). These results were similar in the subgroup of patients treated with ARS-inhibitors. AR-V7 expression was also associated with poor clinical outcomes in patients treated with ARS-inhibitors but no correlation was found between HER2 and AR-V7 expression. In patients treated with ARS-inhibitors, multivariate analyses revealed that the prognostic impact of HER2 status on PSA-PFS was independent of AR-V7 expression and of the presence of CTCs.
Conclusions
Here we report for the first time that HER2 expression in CTCs of patients with mCRPC is associated with shorter PSA-PFS and radiological-PFS. HER2 expression in CTCs may be a novel prognostic marker for mCRPC and might be a novel targetable marker.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
La ligue contre le cancer.
Disclosure
D. Maillet: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen ; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. All other authors have declared no conflicts of interest.