OS01.5.A Neuron-specific enolase (NSE) and S100 serum levels in patients with active brain metastases from HER2-positive breast cancer treated with trastuzumab-deruxtecan (T-DXd): A biomarker analysis from the TUXEDO-1 trial

Abstract Background T-DXd is a novel antibody-drug conjugate with high activity in HER2-positive metastatic breast cancer. The prospective, single-arm, single-centre phase II TUXEDO-1 trial showed clinically relevant of BC pts active BM an intracranial response rate 73.3%. This biomarker sub-study aimed to investigate changes the extent metastases-induced brain damage patients and without therapy by measuring serum levels two proteins constitutively expressed human measurable upon blood serum: NSE S100. Material Methods We assessed (sNSE) S100 (sS100) total 37 samples drawn at cycles 1, 4 end treatment (EOT) all intent-to-treat population using commercially available ELISA assays. Intracranial radiological was centrally board-certified neuro-radiologist RANO criteria. sNSE sS100 were compared between responders non-responders Mann Whitney U test significance level 0.05. Results At baseline, we detected no significant difference or non-responders, respectively. Baseline median 10.6 ng/ml (interquartile range (IQR) 8.6-12.2) as 12.5 (IQR 12.2-12.9) non-responder group (n.s.). cycle 4, corresponding numbers 8.1 responding 7-11.2) 12.7 respectively (p=0.009). No differences observed groups any time point. Conclusion In showing objective T-Dxd, significantly lower suggesting reduction direct effect. may be useful for longitudinal assessment metastasis burden.