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

携带Ala750_Ile759delinsGlyGly突变的EGFR突变型尿路上皮癌对多种化疗药物具有原发性耐药性,但对奥希替尼敏感:关于EGFR突变及EGFR酪氨酸激酶抑制剂在癌症中的作用的文献综述

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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.

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