(UroToday.com) Dr. Tanya Jindal reports on independent biomarkers predictive of outcomes with enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC), based on an analysis of the UNITE study.
The authors used the established UNITE Urothelial Cancer Network to Investigate Therapeutic Experiences) is a large multi-institutional retrospective cohort study of patients with aUC treated with novel agents and encompasses 16 centers. Their initial experience with using EV was published in 2021.1
As a reminder, EV is an antibody-drug conjugate (ADC) targeting Nectin-4 and is used widely in treatment-refractory aUC, but there is limited data available on biomarkers predictive of EV outcomes.
EV is used for treatment-refractory advanced UC, but there has been documented activity in the first line setting. However, selecting for its use will depend on independent biomarkers, which are currently lacking.
In this analysis, they included patients from the UNITE cohort who were treated with EV monotherapy and had available next generation sequencing (NGS) data.
Assessed biomarkers included:
- Genomic alterations (alts) that were present in ≥5% of pts
- Tumor mutation burden (TMB)
- PD-L1 expression.
They only considered patients for an assessment of ORR (observed response rate) if they had scans after at least 1 EV cycle.
Secondary outcomes included progression-free survival (PFS) and overall survival (OS) from EV start.
From their dataset, they identified 303 patients who were treated with EV monotherapy who also had NGS testing. Of these, 207 had TMB and 146 had PD-L1 data.
Demographics are summarized below:
Median age was 70 and 196 (66%) had pure urothelial histology. 212 (71%) with lower tract primary tumor and many patients (N=204, 67%) had ≥2 prior therapies.
Looking at clinical outcomes, the ORR in this cohort of eligible patients was 53% (140/264) while median PFS was 6.0 mos and median OS was 13.1 mos.
On univariate analysis, longer OS was associated with higher Hgb, albumin, and GFR (>30cc/min), lower neutrophil to lymphocyte ratio, older age, and absence of liver mets.
On multivariate analysis, they included these variables along with histology as covariates. In multivariate models, better outcomes were associated with alts in ERBB2, KDM6A and PIK3CA, while inferior outcomes with low TMB (<10 Mut/Mb) and high PD-L1 (CPS ≥ 10).
In this important ongoing work using the UNITE dataset, the authors continue to provide important insights into the real world outcomes of EV therapy and potential markers that can be used to select patients for good response.
First, their real-world data outcomes are comparable to trial data for EV monotherapy.
In their multivariable analysis, they identified several potential biomarkers independently associated with EV treatment outcomes. Longer OS was associated with ERBB2 and KDM6A alts, low PD-L1, and high TMB.
They acknowledged the limitations, many of which are inherent to a large real-world dataset including lack of central scan review, patient selection, and confounding biases.
Presented by: Tanya Jindal, BS, BA, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Franciso, CA
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis, @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
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