# EGFR-Mutant Urothelial Carcinoma Harboring an Ala750_Ile759delinsGlyGly Alteration with a Primary Resistance to Polychemotherapy and a Sensitivity to Osimertinib: A Literature Review on EGFR Alterations and Response to EGFR Tyrosine Kinase Inhibitors in Cancers

## TL;DR

A rare case of EGFR-mutant urothelial carcinoma in a young woman showed resistance to chemotherapy but responded to osimertinib, a targeted therapy.

## Contribution

This case report highlights a novel EGFR mutation in urothelial carcinoma and its sensitivity to osimertinib.

## Key findings

- A 35-year-old woman with EGFR-mutant urothelial carcinoma showed a 5-month response to osimertinib.
- The patient had primary resistance to polychemotherapy but responded to a third-generation EGFR tyrosine kinase inhibitor.
- This case suggests potential therapeutic benefit of osimertinib in rare EGFR-mutant urothelial carcinoma.

## Abstract

Urothelial carcinoma is three to four times more common in men than in women, with a 73-year old mean age at diagnosis which is older than the average age at diagnosis of all cancers. Urothelial carcinoma is rare in people under 40 years of age. Smoking, exposure to industrial chemicals, and family history influence the development of bladder cancer, but age remains one of the most important risk factors. It is well established that women are more likely to be diagnosed with an advanced disease, impacting the prognosis and a higher stage-for-stage mortality compared to men. A gender difference is also observed when considering molecular features; for example, there a higher male/female ratio in Fibroblast Growth Factor Receptor 3 (FGFR3)-mutated bladder cancer. Epidermal Growth Factor Receptor (EGFR) amplifications, which are roughly depicted in 25–50% of urothelial carcinoma, have been correlated with a worse prognosis. Genomic alterations of clinical interest are mainly Human Epidermal Growth Factor Receptor 2 mutations and amplifications, as well as FGFR 3 alterations; however, no EGFR mutation has been routinely reported despite the frequency of its amplifications. Recurrently, no targeted inhibitors have demonstrated a benefit compared to platinum-based chemotherapy. We report a rare case of a 35-year-old woman presenting bone, hepatic, and lymph node metastatic urothelial carcinoma, harboring a deletion of 24 nucleotides in exon 19 of the EGFR gene with a 5-month response to osimertinib, a third-generation EGFR tyrosine kinase inhibitor.