(UroToday.com) In this rapid abstract session, Tanya Jindal presented on behalf of the UNITE study collaborators and helped identify potential biomarkers of response to enfortumab vedotin (EV) in patients with advanced urothelial carcinoma.
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.
The authors investigated potential biomarkers of response to EV in a patient cohort in the UNITE dataset. 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 and 592 patients to-date. Their initial experience with using EV was published in 2021.1
In this abstract, they specifically looked at genetic biomarkers of response from available next-generation sequencing (NGS) testing. Assessed biomarkers included:
Observed response (ORR) was determined by investigators for evaluable patients with scans after ≥1 dose of EV. ORRs were compared using Chi-squared test, while median progression-free and overall survival (mPFS, mOS) from EV start were compared with log-rank test and Cox proportional hazards in pts with and without biomarker presence.
A total of 170 pts had outcomes and NGS data available. Full demographics are seen below:
She highlighted the following:
- 80% had visceral mets, 35% had liver mets
- ~2/3 had 2 or more prior lines of therapy
The primary source of NGS testing was FoundationMedicine, but other sources included Tempus, Oncomine, UCSF500, Guardant 360, etc.
For all 170 patients, ORR 47%, median PFS 6 mos, median OS 12 mos and median follow-up was 9.4 months.
But, ORRs were higher in patients with ERBB2 (67% vs 44%; p = 0.05) and TSC1 (68% vs 25%; p=0.04) alts vs wild-type.
Shorter median PFS was noted in pts with CDKN2A, CDKN2B, and MTAP alterations, while longer median OS in patients with high TMB (table and figures)
Two composite biomarkers (seen at the bottom of the table) were also assessed – shorter PFS was seen in both composite groups.
They concluded by noting that in this large, multi-site, retrospective cohort of patients with advanced UC, they identified several potential biomarkers associated with differential outcomes to EV. These findings, upon external validation, may help inform clinical decision making and potential therapy sequencing with available ADCs. Limitations include retrospective nature, pt selection, and confounding biases.
Presented by: Tanya Jindal, Senior Clinical Research Coordinator, HDF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:- Koshkin VS, Henderson N, James M, Natesan D, Freeman D, Nizam A, Su CT, Khaki AR, Osterman CK, Glover MJ, Chiang R, Makrakis D, Talukder R, Lemke E, Olsen TA, Jain J, Jang A, Ali A, Jindal T, Chou J, Friedlander TW, Hoimes C, Basu A, Zakharia Y, Barata PC, Bilen MA, Emamekhoo H, Davis NB, Shah SA, Milowsky MI, Gupta S, Campbell MT, Grivas P, Sonpavde GP, Kilari D, Alva AS. Efficacy of enfortumab vedotin in advanced urothelial cancer: Analysis from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study. Cancer. 2022 Mar 15;128(6):1194-1205. doi: 10.1002/cncr.34057. Epub 2021 Dec 9. PMID: 34882781.
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Exploring Genetic Biomarkers of Response to Enfortumab Vedotin in Advanced Urothelial Carcinoma: Analysis of UNITE Dataset - Tanya Jindal & Vadim Koshkin