Targeted therapies for Bacillus Calmette-Guérin unresponsive nonmuscle-invasive bladder cancer: a narrative review.

Purpose of review: The purpose of this narrative review is to compile the latest available evidence on targeted therapy in the management of Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC).

Recent findings: Several recent studies have reported promising results for anti-fibroblast growth factor receptor (FGFR) (erdafitinib) in patients with advanced or metastatic urothelial carcinoma with FGFR alterations. These findings support the exploration of targeted therapies, including tyrosine kinase inhibitors (anti-FGFR and anti-vascular endothelial growth factor (VEGF)), mTOR inhibitors, and EpCAM inhibitors at an earlier stage of the disease to avoid or delay radical cystectomy.

Summary: The THOR-2 study demonstrated promising results for oral Erdafitinib in 73 high-risk BCG-unresponsive pTa/pT1 patients, showing 6 and 12-month recurrence-free survival rates of 96 and 77%, respectively. However, it was associated with notable adverse events (100%, including 22% serious). Other targeted therapies, such as Dovitinib (FGFR inhibitor), Sunitinib (VEGF inhibitor), and Everolimus (mTOR inhibitor), were assessed in three phase II studies, yielding disease-free survival rates between 8 and 44% over 3-12 months. Additionally, in a recent phase 3 trial involving 134 patients with BCG-unresponsive NMIBC, Oportuzumab Monatox (an EpCAM inhibitor) demonstrated a complete response rate of 40% at 3 months and a median response duration of 9.4 months.