Highlights
- •Genomic sequencing has gained a foothold in routine clinical care for metastatic urothelial cancer (mUC) and may provide prognostic or predictive value with immune checkpoint therapy (ICI) therapy.
- •Telomerase reverse transcriptase (TERT) promoter mutations are amongst the most commonly detected mutations in mUC and have been associated with ICI response in a prior study.
- •ATM mutations in particular are associated with poor outcomes in mUC, however there is data to suggest that DNA damage repair mutations may portend better responses with ICI.
- •Our study found no significant difference in outcomes with TERT mutations, while ATM mutations were significantly associated with poorer outcomes.
Abstract
Background
Recently data suggest that telomerase reverse transcripatase (TERT) promoter mutations portend superior outcomes with immune checkpoint inhibitor (ICI)
therapy in mUC. In our retrospective analysis from 2 tertiary cancer centers, we assessed
the predictive role of TERT mutations along with other parameters.
Methods
Patient registries were queried for patients treated with ICI for mUC with available
genomic and clinical data. Select clinical and laboratory parameters, in addition
to primary tumor site, histology, treatment modality, and setting were recorded. Tumor
mutational burden (TMB), and mutational status of TERT, CDKN2A, CDKN2B, TMB, TP53, RB1, KMT2D, ARID1A, ERBB2, KDM6A, PIK3CA, FGFR3, and ATM were noted. Univariate analysis of significance concerning overall response rate
(ORR), progression-free survival (PFS), and overall survival (OS) was conducted.
Results
In total, 113 patients were found to meet inclusion criteria. In our study, ORR was
55%, median PFS was 5.1 months (0.2-71.8), and median OS was 13.4 months (0.2-84.8).
On univariate analysis, female sex, NLR>5, and ATM mutation were associated with inferior PFS and OS, whereas upper tract primary disease
and ECOG score ≥ 2 were associated with worse OS. On multivariate analysis, NLR >5
was associated with worse PFS and OS whereas upper tract primary disease, albumin
<3.4 g/dL, hemoglobin <10 g/dL and ATM mutation were significantly associated with worse OS on multivariate analysis. No
significant differences were seen in ORR, PFS, or OS regarding TERT promoter mutations.
Conclusion
TERT promoter mutations were not significantly associated with any difference in outcome
in patients treated with ICI.
Keywords
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Article info
Publication history
Published online: November 17, 2022
Accepted:
November 14,
2022
Received in revised form:
November 8,
2022
Received:
April 25,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc.
