Understanding diversity and disparities in a real-world locally advanced/metastatic urothelial carcinoma (la/mUC): Clinical characteristics, genomic landscape, and self-reported social determinants of health (SDOH).
Authors: Alimohamed Nimira S. , Gibson Amanda Williams , Dean Michelle Liane , Xu Tracy Jing , Murali Megha , Banjaw Roba Kebebew , Basappa Naveen S. , Bismar Tarek A. , Dehar Navdeep , Karim Safiya , Kolinsky Michael Paul , Heng Daniel Yick Chin , Lee-Ying Richard M. , Navani Vishal , North Scott A. , Ruether Joseph D. , Taleb Amina , Osborne Brendan J.W. , Bose Pinaki , Yip Steven 
Published: February 2025

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Background:
Fibroblast growth factor receptor (FGFR) inhibitor therapy improves overall survival in LA/mUC patients with FGFR 2/3 alterations and prior systemic therapy including immune checkpoint inhibitors (ICI). The current treatment landscape is rapidly evolving with inequities in molecular testing and access to novel therapies. In the real-world, the genomic landscape, treatment patterns, and outcomes in LA/mUC have yet to be established. In this multicenter prospective cohort study, we examined the RW treatment patterns, outcomes, genomic profile, diversity, and SDOH in pts with LA/mUC.
Methods:
In this LA/mUC cohort, we assessed baseline characteristics, self-reported SDOH, clinical management patterns, and treatment outcomes (PFS, OS). Comprehensive genomic profiling (CGP), including
FGFR1-4,
of DNA and RNA from archived FFPE tissue were analyzed.
Results:
42 pts with LA/mUC were enrolled from Apr – Sept 2024 (79% bladder; 21% upper tract). 93% (39/42) had distant metastases (18% visceral). Median age at diagnosis was 69 yrs and 79% were male. 23 (62%) completed a questionnaire. 96% self-reported as White/Caucasian, 4% as Indigenous. 26% live in a rural setting >1 hour from a cancer centre. 47% report financial stress. 30% report a family history of Lynch Syndrome related malignancies. In 35 pts who underwent CGP, 11 pts (31%) had FGFR alterations, comprised of FGFR1-3 fusions, amplification, or mutations (Table 1). 88% (37/42) of pts received first-line (1L) therapy, primarily CTx (78%), and 1 pt received an FGFR-inhibitor. 62% (23/37) received 2L therapy (83% ICI, of which 68% was maintenance avelumab). 8 pts received 3L (63% (5/8) antibody drug conjugate [ADC]). 2 pts received 4L (n=1 ADC, n=1 CTx); 1 pt received 5L (ICI). Median progression free survival (mPFS) was 7.6 mo (95% CI: 5.1 – 22.5), 6.6 mo [95% CI: 2.5 – NR] and 6.9 mo [2.1 – NR], for 1L, 2L, 3L, respectively, but not reached for 4L and 5L. 88% are alive with a median follow-up of 10.3 months. Overall survival was not yet reached.
Conclusions:
This RW analysis of pts with LA/mUC provides valuable insights into the genomic landscape, clinical characteristics, and SDOH within this population. The presence of targetable genomic alterations underscores the necessity for an equitable precision medicine approach in diverse LA/mUC pt populations to optimize outcomes. This study demonstrates the feasibility of collection of a comprehensive array of data and samples to guide a management for patients with LA/mUC.

NGS results.

FGFR
Alteration (n=11)

Number (%)

FGFR1
amp (borderline)

1 (9)

FGFR1::TBC1D22A fusion

1 (9)

FGFR2::USP11 fusion

1 (9)

FGFR3
mutation

3 (27)

FGFR3::FGFR1 fusion

2 (18)

Insufficient sample
3 (27)