Daf da good stuff.
The Study: Erdawhotinib? No, that’s still in phase 1. Erdafitinib is an FGFR1-4 tyrosine kinase inhibitor (TKI) that was tested in 100 patients with unresectable or metastatic urothelial carcinoma harboring alterations in the fibroblast growth factor receptor (FGFR) and progressing on prior chemo. The rationale for this phase 2 trial BLC2001 is that urothelial carcinomas can be classified into two broad molecular categories: basal and luminal. Akin to breast cancer, the luminal-type appears to have less immunogenicity and a lower response rate to immunotherapy. However, it is characterized by higher rates of FGFR mutations—hence the current trial where patients had to have either a FGFR3 mutation or a FGFR2/3 fusion. The response rate with erdafitinib was 40%, which surpassed the efficacy signal of 25%, and the median duration of response was nearly 6 months. However, even more patients experienced a grade 3+ toxicity, the most common being stomatitis and hyponatremia. In addition, over three-quarters of patients experienced hypophosphatemia, a notorious issue with FGFR-TKIs.
TBL: While erdafitinib joins a growing list of treatment options for progressing urothelial carcinoma, it carves itself a nice molecular niche for luminal-type disease. | Loriot, N Engl J Med 2019