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
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
2661 - Tumor stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumors.
Presenter: Myriam Fabre
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract