Abstract 208P
Background
Enzalutamide (enz), has demonstrated substantial preclinical anti-tumour activity in both triple-negative breast cancer (TNBC) and oestrogen receptor positive (ER+ve) breast cancer (BC). ARB was a short-term preoperative window of opportunity (WOO) study that aimed to assess the anti-tumour effects of enz in ER+ve BC and TNBC.
Methods
An ER+ve BC cohort included 194 women, randomised 2:1 to enzalutamide + exemestane (enz+exe) (130 pts) or exemestane (exe) alone (64 pts). Patients (pts) were stratified by histological grade, level of ER expression and geographic region. An androgen receptor positive (AR+ve), TNBC cohort included 27 women treated with enz alone. All pts were newly diagnosed, with a tumour size ≥1cm and ECOG PS 0-2. The primary endpoint for the ER+ve cohort was inhibition of tumour-cell proliferation, measured by change in Ki67 expression, determined centrally. For the AR+ve cohort, the primary endpoint was individual anti-proliferative response (≥50% fall in Ki67 expression). Analyses presented are for the per-protocol population. Secondary endpoints included induction of apoptosis (Caspase3) and safety. Biomarker exploratory endpoints analysis is ongoing.
Results
Baseline (BL) characteristics were similar between both study arms. The incidence of related AE’s were consistent and as expected for the study drugs. In the ER+ve cohort, geometric mean post-treatment percentage (%) reduction of Ki67 was 56% (95% CI, 47%-63%) for exe alone and 60% (95% CI, 53%-66%) for enz+exe. Ki67-response was 54% for exe alone and 63% for enz+exe (one-sided p-value=0.19). Planned sub analyses showed a significant interaction of response to enz+exe with molecular subtype. Pts with Luminal A (LumA) tumours had a higher Ki67 response with enz+exe compared to exe alone (64% vs 38%, one-sided p-value=0.03). Ki67 response was similar for both treatments for LumB tumours (enz+exe, 63%; exe alone, 71%, one-sided p-value=0.36). In the TNBC AR+ve cohort treated with enz alone, geometric mean post-treatment % reduction of Ki67 was 8% (95% CI, -8%-21%). Ki67-response was 5%.
Conclusions
No difference was seen overall in inhibition of Ki67 expression after treatment with enz. However, subgroup analysis did show a possible response in LumA pts.
Clinical trial identification
NCT02676986.
Editorial acknowledgement
Legal entity responsible for the study
Queen Mary University of London, UK.
Funding
Astellas.
Disclosure
P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Oncogenex; Financial Interests, Institutional, Research Grant: Roche; Other, Spouse - Employee: Roche. D. Wheatley: Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer. M. Thill: Financial Interests, Advisory Board: Amgen; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Aurikamed; Financial Interests, Advisory Board: Becton/Dickinson; Financial Interests, Advisory Board: Biom‘Up; Financial Interests, Advisory Board: Celgene; Financial Interests, Advisory Board: ClearCut; Financial Interests, Advisory Board: Clovis; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: Eisai; Financial Interests, Advisory Board: Exact Sciences; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Endomagnetics; Financial Interests, Institutional, Research Grant: Exact Sciences. G. Viale: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Ventana; Financial Interests, Personal, Advisory Board: Dako Agilent; Financial Interests, Personal, Other, Consultancy: Menarini; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Cepheid; Financial Interests, Institutional, Research Grant: Dako Agilent; Financial Interests, Institutional, Research Grant: Ventana. J. Cortés: Financial Interests, Personal, Advisory Board: 4D Pharma PLC; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: Bioasis; Financial Interests, Personal, Advisory Board: Biothera; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Advisory Board: Cellestia; Financial Interests, Personal, Advisory Board: Clovis oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Erytech; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Kyowa Kyrin; Financial Interests, Personal, Advisory Board: Leuko; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Polyphor; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Samsung Bioepis; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Research Grant: Bayer healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Guardanth health; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma B; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Financial Interests, Institutional, Research Grant: Roche. S. Kümmel: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Genomic Health; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: pfmmedical; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Somatex; Financial Interests, Personal, Invited Speaker: Sonoscape; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche Pharma; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: pfmmedical; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Somatex; Other, Leadership Role: WSG; Other, Leadership Role: AGO. All other authors have declared no conflicts of interest.