TERT promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor

Abstract

BackgroundImmune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.MethodsWe undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.ResultsWe identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).ConclusionsThe presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.

The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

“…A 3.5 gr/dL albumin cut-off was most frequently used in the included studies (n = 20) (Dercle et al, 2016;Bigot et al, 2017;Mezquita et al, 2018;Formica et al, 2020;Jiang et al, 2020;Kitadai et al, 2020;Lee et al, 2020;Takada et al, 2020;Awada et al, 2021;Brown et al, 2021;Khaki et al, 2021;Morimoto et al, 2021;Ng et al, 2021;Onn et al, 2021;Pu et al, 2021;Ruiz-Bañobre et al, 2021;Sato et al, 2021;Stares et al, 2021;Tokuyama et al, 2021;Assié et al, 2022;Chen et al, 2022;Kim et al, 2022;Li et al, 2022;Schneider et al, 2022;Stares et al, 2022;Wu et al, 2022;Yoo et al, 2022;Zhang et al, 2022), while eight studies evaluated the effect of albumin levels on survival by using albumin as a continuous measure (Svaton et al, 2018;Ichiki et al, 2019;Cantini et al, 2020;Swami et al, 2020;de Kouchkovsky et al, 2021;Ke et al, 2021;Abuhelwa et al, 2022;Guo et al, 2022). All but two studies reported HRs for OS (Stroup et al, 2000;Schneider et al, 2022;Zhang et al, 2022), while data for PFS was available in 15 studies (Stroup et al, 200...…”

Repeat Treatment of Patients With Advanced Urothelial Carcinoma With Immune Checkpoint Inhibitors Following Prior Progression on a Checkpoint Inhibitor Regimen: A Case Series

“…For most of these patients, status of putative biomarkers including PD-L1, TMB and alterations potentially predictive of IO response in aUC were also unknown. [22][23][24] The incidence of irAEs with ICI treatment as described in this series was also not clearly associated with specific treatment outcomes. Nevertheless, this case series represents an important initial hypothesisgenerating effort that future studies can build on.…”

A Novel Risk Model for lncRNAs Associated with Oxidative Stress Predicts Prognosis of Bladder Cancer

“…The development of targeted drugs based on risk models may improve the treatment effect of NMIBC and MIBC. Immune checkpoint inhibitors were a potential cancer treatment that blocks key molecules and showed excellent anticancer efficacy, particularly in revolutionizing the clinical progression of metastatic and locally advanced BCa [ 50 , 51 ].…”