Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors.

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.

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.

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.

TERT promoter mutations were not significantly associated with any difference in outcome in patients treated with ICI.

Clinical genitourinary cancer. 2022 Nov 18 [Epub ahead of print]

Neal S Chawla, Nicolas Sayegh, Nishita Tripathi, Ameish Govindarajan, Zeynep B Zengin, Errol J Phillip, Nazli Dizman, Luis Meza, Ramya Muddasani, Alexander Chehrazi-Raffle, Jasnoor Malhotra, JoAnn Hsu, Neeraj Agarwal, Sumanta K Pal, Abhishek Tripathi

Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA., Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT., School of Medicine, University of California San Francisco, San Francisco, CA., Yale University School of Medicine, New Haven, CT., Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA. Electronic address: .