Abstract 2870
Background
Treatment response to androgen deprivation therapy (ADT) in androgen receptor (AR)-positive salivary duct carcinoma (SDC) is 18-50%. The cause of ADT-resistance is unknown. We aim to predict treatment response through analysis of functional AR-pathway activity.
Methods
Patients who received palliative ADT (n = 28) for locally recurrent or metastatic SDC were selected. ADT consisted of bicalutamide or combined androgen blockade. AR-pathway analysis was performed in all patients. For this, RNA was extracted from annotated, formalin-fixed paraffin embedded sections from tumor tissue prior to treatment. For quantitative measurement of functional AR pathway activity, mRNA expression of the AR pathway target genes was measured using one-step RT-qPCR, and a pathway activity score between 0 and 100 was provided (Verhaegh et al, Cancer Res. 2014). Patients were analyzed for treatment response, progression free survival (PFS) and overall survival (OS).
Results
AR pathway activity score was divided in tertiles. Patients with highest AR activity had the longest progression free survival (PFS) and overall survival (OS) upon ADT treatment. Partial responders (PR) were only observed in the group with the highest AR activity (n = 3, p = 0.0267, two-sided Fisher exact), while highest incidence of progressive disease (PD) was found in the lowest AR activity group.Table: 1079P
| AR-pathway activity (range) | Response (number of patients) | Median PFS (months) | Median OS (months) | |||
|---|---|---|---|---|---|---|
| Tertile 1 | 33.10-43.55 | 0 PR | 1 SD | 9 PD | 2 | 12 |
| Tertile 2 | 43.71-50.35 | 0 PR | 2 SD | 7 PD | 2 | 13 |
| Tertile 3 | 51.91-65.58 | 3 PR | 4 SD | 2 PD | 5 | 33 |
Conclusions
Functional AR pathway activity measured by this new method was predictive for clinical response to ADT in this small retrospective SDC cohort. Extended validation of clinical utility in a larger patient cohort is in preparation.
Clinical trial identification
Legal entity responsible for the study
Radboud University Medical Center, Nijmegen, the Netherlands.
Funding
Dutch Salivary Gland Cancer Patient Platform and Radboud Oncology Fund.
Editorial Acknowledgement
Disclosure
D. van Strijp, J.B.A. van Zon, A. van de Stolpe: Employee, corporate research funding: Philips Research. S. Neerken: Employee, corporate research funding: Philips Healthworks. All other authors have declared no conflicts of interest.
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