Investigators observed differing response rates between patients with upper tract primaries relative to patients with bladder primaries. They hypothesize that differences in the somatic mutational landscape between upper tract and lower tract tumors may explain the observed difference in response to FGFR targeted therapy. Specifically, of 67 evaluable patients, 59 had lower tract primaries, among whom infigratinib achieved a modest 22.0% response rate. However, among the 8 patients with upper tract primaries – noting the limitations of the small sample size – investigators identified 3 PRs and 1 CR for an overall response rate of 50.0%
Sequencing of the FGFR3 gene identified a predominance of the R248C mutation among upper tract tumors in which it comprises 50% of the FGFR3 alterations relative to just 12% of the lower tract primaries. Furthermore, the majority (59%) of lower tract tumors harbored the S249C relative to just 38% of upper tract primaries.
Commensurate with the higher objective response rate, patients with upper tract primaries achieved significantly longer progression-free (8.5 months versus 3.7 months) and overall survival (21.8 months versus 3.7 months) relative to patients with bladder primary bladder cancer.
Finally, investigators sought to further characterize the mutational landscape of these tumors utilizing circulating cell-free DNA. In particular, it was noted that lower tract tumors exhibit a higher variant allelic frequency, perhaps alluding to distinct tumor biology. Finally, the variant allelic frequency was significantly higher in tumor tissue relative to in circulating cell-free DNA, suggesting differences between the metastasizing cell populations relative to the bulk tumor.
Given the impressive response rate to infigratinib among patients with upper tract urothelial carcinoma, a phase III adjuvant trial is planned.
Presented by: Nazli Dizman, MD, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA
Written by: Michael Lattanzi, MD, Internal Medicine Resident, Department of Medicine, NYU School of Medicine, @MikeLattanzi at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
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