Meeting
2023 ASCO Genitourinary Cancers Symposium
Association of biomarkers and outcomes in patients (pts) with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs).
Authors
Kevin R Reyes
University of California, San Francisco, San Francisco, CA
Kevin R Reyes , Li Zhang , Xiaolin Zhu , Tanya Jindal , Prianka Deshmukh , Ivan de Kouchkovsky , Vipul Kumar , Edward Maldonado , Daniel H Kwon , Emily Chan , Sima P. Porten , Hala Borno , Rohit Bose , Arpita Desai , Rahul Raj Aggarwal , Eric Jay Small , Lawrence Fong , Jonathan Chou , Terence W. Friedlander , Vadim S Koshkin
Organizations
University of California, San Francisco, San Francisco, CA, UCSF Hem/Onc Fellowship, San Francisco, CA, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, University of California San Francisco, San Francisco, CA, UCSF, San Francisco, CA, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Division of Hematology and Oncology, University of California, San Francisco, CA, University of California, San Francisco Medical Center, San Francisco, CA
Research Funding
No funding received
None.
Background: ICIs form the backbone of treatment for mUC. However, only a minority of pts benefit and additional biomarkers of ICI response are needed. Methods: In our institution, we identified mUC pts treated with ICI monotherapy who had next generation sequencing (NGS). Somatic alterations present in ≥10% of pts (ARID1A, CCND1, CDKN2A, CDKN2B, ERBB2, FGF3, FGF4, FGF19, FGFR3, KDM6A, MDM2, MLL2, PIK3CA, RB1, TERTp, TP53, TSC1), as well as DNA-damage response (DDR) alterations and tumor mutational burden (TMB) were analyzed as biomarkers. These biomarkers were individually evaluated in separate multivariate models while accounting for clinical factors including age, BMI, ECOG PS, primary tumor location, histology, hemoglobin, neutrophil to lymphocyte ratio and albumin. Multivariate cox regression and logistic regression models were used to measure hazard ratios (HR) and odds ratios (OR) for overall survival (OS), progression-free survival (PFS) and observed response rate (ORR). Results: Among 152 mUC ICI-treated pts, 107 had NGS data (FoundationOne, UCSF500, Strata), including 85 with TMB data. For the 107 pts with NGS, median age was 70 yrs, majority were male (69, 64%), Caucasian (70, 65%), had pure urothelial histology (57, 53%), and had first-line ICI (55, 51%). ORR was 35%, median PFS was 3.9 mos (95% CI: 2.6-7.5 mos), and median OS was 17.4 mos (95% CI: 14.1-30.6 mos). Biomarkers associated with improved outcomes to ICI, independent of relevant clinical factors, included alterations in ARID1A and DDR, as well as high TMB (>10 Mut/Mb). Inferior outcomes were seen in pts with CDKN2B, KDM6A, FGF3, FGF4, and FGF19 alterations (Table). Conclusions: In this large retrospective multivariate analysis controlling for clinical factors in ICI-treated mUC pts, we found multiple biomarkers associated with improved or inferior outcomes. These hypothesis-generating findings can inform clinical decision making and trial design for mUC pts treated with ICIs, and should be validated in larger cohorts.
| Biomarker | Pts w/ Biomarker N (%) | OS: HR (95% CI, p-value) | PFS: HR (95% CI, p-value) | ORR: OR (95% CI, p-value) |
|---|---|---|---|---|
| ARID1A | 26 (24%) | 0.45 (0.2-1.2, p=0.11) | 0.27 (0.1-0.6, p<0.01) | 7.69 (1.6-51.1, p=0.02) |
| DDR* | 17 (16%) | 0.35 (0.1-1.0, p=0.05) | 0.39 (0.2-1.0, p=0.05) | 4.82 (0.8-40.4, p=0.11) |
| CDKN2B | 34 (32%) | 1.83 (0.9-3.9, p=0.11) | 1.88 (1.0-3.5, p=0.05) | 0.27 (0.1-1.3, p=0.12) |
| KDM6A | 23 (21%) | 1.49 (0.6-3.5, p=0.36) | 2.41 (1.2-4.8, p=0.01) | 0.47 (0.1-2.0, p=0.31) |
| FGF19 | 13 (12%) | 7.71 (2.4-25.0, p<0.01) | 3.27 (1.1-9.7, p=0.03) | 0.86 (0.1-9.5, p=0.90) |
| FGF4 | 13 (12%) | 5.32 (1.7-16.4, p<0.01) | 3.76 (1.3-10.7, p=0.01) | 0.20 (0.01-2.3, p=0.24) |
| FGF3 | 12 (11%) | 5.32 (1.7-16.4, p<0.01) | 3.76 (1.3-10.7, p=0.01) | 0.20 (0.01-2.3, p=0.24) |
| TMB high | 47 (55%) | 0.59 (0.3-1.4, p=0.23) | 0.43 (0.2-0.9, p=0.03) | 5.26 (1.1-30.9, p=0.04) |
*DDR alterations: ATM, BARD1, BRCA1, BRCA2, CDK12, CHEK2, and PALB2.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Details
Session Type
Poster Session
Session Title
Poster Session B: Prostate Cancer and Urothelial Carcinoma
Track
Urothelial Carcinoma,Prostate Cancer - Advanced
Sub Track
Translational Research, Tumor Biology, Biomarkers, and Pathology
Citation
J Clin Oncol 41, 2023 (suppl 6; abstr 532)
DOI
10.1200/JCO.2023.41.6_suppl.532
Abstract #
532
Poster Bd #
L15
Abstract Disclosures
Similar Abstracts
Abstract
2024 ASCO Genitourinary Cancers Symposium
Genomic correlates of response and resistance to immune checkpoint inhibitors (ICI) in patients with metastatic urothelial carcinoma (mUC) in a real-world setting.
First Author: Nikhil Pramod
Abstract
2022 ASCO Annual Meeting
Association between tumor mutational burden (TMB) and mutational profile and its effect on overall survival: A post hoc analysis of patients with TMB-high and TMB-low metastatic cancer treated with immune checkpoint inhibitors (ICI).
First Author: Camila Bragança Xavier
Abstract
2023 ASCO Genitourinary Cancers Symposium
Biomarkers of response to enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study.
First Author: Tanya Jindal
Abstract
2023 ASCO Genitourinary Cancers Symposium
Biomarkers of response to enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study.
First Author: Tanya Jindal