Case Report: Targeting EGFR exon 20 insertion and MTAP loss in refractory metastatic upper tract urothelial carcinoma

Vollständiger Abstract

Worum geht es in dieser Arbeit?

This case report illustrates the use of amivantamab in combination with pemetrexed-based chemotherapy for the treatment of a 60-year-old man with refractory metastatic upper tract urothelial carcinoma (UTUC) with epidermal growth factor receptor (EGFR) exon 20 insertion (D770_N771insGF) and methylthioadenosine phosphorylase (MTAP) loss identified in both the primary left nephroureterectomy tissue and lung metastasis biopsy. The patient, who had progressed on five prior lines of therapy including platinum-based chemotherapy, immunotherapy, and antibody-drug conjugates, attained a sustained partial response with favourable tolerability before eventual disease progression with brain metastasis. This case is unique because of the uncommon molecular profile, with an EGFR exon 20 insertion observed in only 0.7% of urothelial carcinomas, which highlights the potential for repurposing targeted therapies developed for other malignancies in biomarker-defined subgroups of UTUC. This case report highlights the significance of next-generation sequencing in uncovering rare therapeutic targets, the potential of synthetic lethality approaches in MTAP-deficient tumours, and supports further research to explore molecular-based cancer classification and treatment strategies in precision oncology.