FGFR3 Mutations Possible Therapeutic Target in Bladder Cancer

May 10, 2016

A new study found that FGFR3 mutation status could be used to guide anti-FGFR3 therapy in bladder cancer, as the mutation is homogeneous in radical cystectomy specimens and cancer-positive lymph nodes.

A new study found that FGFR3 mutation status could be used to guide anti-FGFR3 therapy in bladder cancer, as the mutation is homogeneous in radical cystectomy specimens and cancer-positive lymph nodes (LN+). Assessment by transurethral resection should be done on the deeper part of tumors, according to the study.

“Preclinical in-vitro and in-vivo data show that anti-FGFR3 therapy slows down tumor growth, especially in FGFR3-mutated tumors,” wrote study authors led by Bas W. G. van Rhijn, MD, of the Netherlands Cancer Institute in Amsterdam. “However, the heterogeneity of FGFR3 status within a tumor or a patient has not been adequately addressed and may negatively impact therapeutic response.”

The new study included analysis of tumor samples obtained via transurethral resection (61 patients) or radical cystectomy (614 patients) with corresponding LN+ (201 patients). The results were published online ahead of print in Annals of Oncology.

In the transurethral resection cohort, FGFR3 mutations were found in 13 of 34 T1 patients and in 8 of 27 the ≥ T2 patients. In the T1 patients, there was no discordance found between paired superficial and deep parts of the tumor, whereas half of the ≥ T2 tumor samples showed discordance; of those, only 4 of 8 had an FGFR3 mutation in the deeper part of the tumor. “The deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered,” the authors wrote.

Among the radical cystectomy samples, FGFR3 mutations occurred in 67 of them (11%); 54 of those were pN0. The presence of a mutation was significantly associated with lower pT-stage (P < .001) and with pN0 (P < .001) at the time of radical cystectomy.

In the 201 paired radical cystectomy/LN+ samples, the same FGFR3 mutation was found in both the cystectomy and in the LN+ specimen. There were no instances of discordance between these samples, for a specificity of 100%. In total, 5% of the paired samples had a mutation, and 191 of the pairs (95%) were both wild type.

“Our data on tumor heterogeneity suggest that personalized anti-FGFR3 therapy may improve bladder cancer treatment for a relatively small, well-selected subgroup of invasive [urothelial carcinoma of the bladder] patients,” the researchers concluded. “Studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.”