High expression level of ERBB2 and efficacy of trastuzumab deruxtecan in desmoplastic small round cell tumour: a monocentric case series report

Abstract

Background

Desmoplastic small round cell tumours (DSRCTs) represent an ultra-rare subtype of soft tissue sarcoma characterized by a recurrent EWSR1::WT1 oncogenic translocation. Considered as an extremely aggressive cancer, the prognosis remains poor with a median overall survival not exceeding 24-36 months and a 5-year survival <10%.

Patients and methods

We analysed ERBB2/human epidermal growth factor receptor 2 (HER2) expression levels in a series of 13 DSRCT patients, using whole-exome RNA sequencing on formalin-fixed paraffin-embedded samples from a local biopathological database. In addition, a retrospective case series describes the clinical outcome of three successive DSRCT patients treated with trastuzumab deruxtecan (T-DXd).

Results

The gene expression analysis demonstrated a consistent high RNA expression level of ERBB2 in DSRCT, with elevated levels [>5 log2(transcripts per million + 1)] across all samples of the cohort and the expression level was the highest compared with all other sarcoma subtypes. In addition to these results, T-DXd showed a marked activity in all three DSRCT patients who presented with metastatic disease refractory to previous standard chemotherapy. So far, the treatment has been overall well tolerated and is currently pursued in the three patients (duration of response >3 months for all three), which warrants additional investigation.

Conclusions

This case series presents a major information, suggesting that HER2 is a therapeutic target in DSRCT and T-DXd might represent a novel therapeutic option. Those results require to be rapidly shared with the scientific community and confirmed in a prospective clinical trial in this context of very poor prognosis disease and urgent unmet need.