Abstract 5574
Background
The role of the androgen receptor (AR) in breast cancer (BC) is not fully elucidated. TRIO030 was conducted to identify molecular changes in BC tissue following short-term exposure to darolutamide (DAR), a new next-generation AR antagonist.
Methods
TRIO030 was a multicenter, tissue-acquisition trial in women with treatment-naïve early BC, T ≥ 1.0 cm, N0-1. Primary objective: identify molecular alterations in BC tissue following preoperative exposure to DAR (600mg bid for 14-35 days). Formalin-fixed paraffin-embedded (FFPE) blocks and fresh frozen tissue (FFT) were collected before DAR and at surgery (or pre neoadjuvant therapy). AR, ER, PgR, HER2, Ki67, Cytokeratin 5-6 were assessed by IHC. Gene expression microarray (GEx) and Reverse Phase Protein Analysis (RPPA) were done on FFT. Differentially expressed genes (DEGs) were found by ANOVA from an integrated gene expression analysis software (Resolver). A gene enrichment search by Gene Ontology (GO) analysis was done using Database for Annotation, Visualization and Integrated Discovery (DAVID).
Results
36 patients (pt) (median age 61.5) were enrolled (20 HR+, 7 TNBC, and 9 HER2+ per central lab). Median duration of DAR was 14.5 days. 32 pts were evaluable by RPPA, 31 by GEx. Based on AR level changes in both RPPA and GEx in pre vs. post-DAR samples, cases were grouped: AR upregulated (≥1.2 fold increase, n = 14), AR downregulated (≥1.2 fold decrease, n = 11), AR unchanged (n = 6). 233 unique DEGs were detected with 84 identified as forming two GEx profiles among the 3 AR groups. GO analysis revealed that DEGs profiles were enriched in an immune (IMM) signature or cell proliferation (CP) signature which were anti-correlated (e.g., if CP is upregulated, IMM is down). No correlation between AR groups and BC subtypes was found. One pt had a grade 3-4 adverse event (non-serious ALT-AST increase).
Conclusions
TRIO030 suggests an association between DAR and immune regulation genes. There was no association between pre/post-DAR AR level changes and BC subtype. Future studies will likely be needed to further investigate the role for AR blockade in BC as well as the mechanism of action for DAR at molecular level.
Clinical trial identification
2016-004151-79.
Editorial acknowledgement
Legal entity responsible for the study
Translational Research in Oncology.
Funding
Bayer (provided the study drug), Translational Research in Oncology (not for profit organization, funded other aspects of the trial).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1242 - Monalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data.
Presenter: Roger Cohen
Session: Poster Display session 3
Resources:
Abstract
4703 - Updated results of a phase II study evaluating accelerator-based boron neutron capture therapy (AB-BNCT) with borofalan(10B) (SPM-011) in recurrent squamous cell carcinoma (R-SCC-HN) and recurrent and locally advanced non-SCC (R/LA-nSCC-HN) of the head and neck
Presenter: Katsumi Hirose
Session: Poster Display session 3
Resources:
Abstract
3638 - Phase 3 KEYNOTE-048 Study of First-Line (1L) Pembrolizumab (P) for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Asia vs Non-Asia Subgroup (subgrp) Analysis
Presenter: Makoto Tahara
Session: Poster Display session 3
Resources:
Abstract
2954 - Integrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
3629 - First line versus second line immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck
Presenter: Caroline Even
Session: Poster Display session 3
Resources:
Abstract
767 - Sensitizing HRAS overexpressing head and neck squamous cell carcinoma (HNSCC) to chemotherapy
Presenter: Theodoros Rampias
Session: Poster Display session 3
Resources:
Abstract
4985 - A Single-Arm, Open-Label, Multicenter, Phase IIIb Clinical Trial with Nivolumab in Subjects with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck.
Presenter: Paolo Bossi
Session: Poster Display session 3
Resources:
Abstract
1564 - Long-term Results of Phase 2 Trial of Reduced Modified Clinical Target Volume in Low-risk Nasopharyngeal Carcinoma Treated with Intensity Modulated Radiotherapy
Presenter: Jingjing Miao
Session: Poster Display session 3
Resources:
Abstract
3356 - To compare two oral mucosa contouring methods in predicting acute oral mucocitis in nasopharyngeal carcinoma treated with helical tomotherapy
Presenter: Yuan-Yuan Chen
Session: Poster Display session 3
Resources:
Abstract
1984 - Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC)
Presenter: Gizem Kaval
Session: Poster Display session 3
Resources:
Abstract