Meeting
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.
Authors
Tanya Jindal
University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
Tanya Jindal , Deepak Kilari , Omar Alhalabi , Amanda Nizam , Ali Raza Khaki , Arnab Basu , Pedro C. Barata , Mehmet Asim Bilen , Sumit Shah , Yousef Zakharia , Matthew I. Milowsky , Joaquim Bellmunt , Hamid Emamekhoo , Nancy B. Davis , Petros Grivas , Shilpa Gupta , Christopher J. Hoimes , Matthew T Campbell , Ajjai Shivaram Alva , Vadim S Koshkin
Organizations
University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, The University of Texas M.D. Anderson Cancer Center, Houston, TX, Cleveland Clinic Foundation, Cleveland, OH, Stanford University, Stanford, CA, University of Alabama at Birmingham, Birmingham, AL, Tulane University, New Orleans, LA, Winship Cancer Institute of Emory University, Atlanta, GA, Stanford Cancer Center, Stanford, CA, University of Iowa, Iowa City, IA, University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, University of Wisconsin, Madison, WI, Vanderbilt University Medical Center, Nashville, TN, University of Washington; Fred Hutchinson Cancer Center, Seattle, WA, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, Duke Cancer Institute, Duke University, Durham, NC, University of Texas MD Anderson Cancer Center, Houston, TX, University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, MI
Research Funding
No funding received
None.
Background: EV, an antibody-drug conjugate (ADC) targeting Nectin-4, is used widely in treatment-refractory aUC, but limited data are available on biomarkers predictive of EV outcomes. We investigated potential biomarkers of response to EV in a pt cohort in the UNITE dataset. Methods: We included the retrospective UNITE study pts from 16 sites, with available next generation sequencing using institutional or commercial platforms, treated with EV alone outside clinical trials. Observed response (ORR) was determined by investigators for evaluable pts with scans after ≥1 dose of EV. Assessed molecular biomarkers included tumor mutation burden (TMB), PD-L1 status, somatic alterations (alts) in ≥ 10% of pts (TERTp, TP53, ARID1A, CDKN2A, CDKN2B, FGFR3, ERBB2, CCND1, KDM6A, MTAP, PIK3CA, RB1, TSC1) and presence of ≥1 DNA damage response mutations (ATM, BARD1, BRCA1, BRCA2, CDK12, CHEK2, PALB2, PPP2R2A, or RAD51B). 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. Results: A total of 170 pts had outcomes and NGS data available. Median age was 70, 133 (78%) were men, 144 (85%) Caucasian, 110 (65%) with pure urothelial histology, 118 (69%) with primary bladder tumor, and 116 (68%) had ≥ 2 lines of therapy before EV. For all pts, ORR 47%, mPFS 6 mos, mOS 12 mos. ORRs were higher in pts with ERBB2 (67% vs 44%; p = 0.05) and TSC1 (68% vs 25%; p=0.04) alts vs wild-type. Shorter mPFS was noted in pts with CDKN2A, CDKN2B, and MTAP alts, and longer mOS in pts with high TMB (table). Conclusions: This large, multi-site, retrospective cohort of pts with aUC 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.
| Alterations | mOS, months (alt present) | mOS, months (alt absent) | HR (95% CI) | p-value | mPFS, months (alt present) | mPFS, months (alt absent) | HR (95% CI) | p-value |
|---|---|---|---|---|---|---|---|---|
| CDKN2A1 (N=39) | 7.8 | 17.3 | 1.5 (0.8 – 2.6) | 0.16 | 4.6 | 6.0 | 1.7 (1.1 – 2.8) | 0.02 |
| CDKN2B1 (N=28) | 7.8 | 17.3 | 1.6 (0.9 – 2.9) | 0.11 | 4.4 | 6.0 | 2.0 (1.2 – 3.4) | <0.01 |
| MTAP1 (N=20) | 7.8 | 17.3 | 1.3 (0.7 – 2.6) | 0.36 | 4.6 | 6.0 | 1.7 (1.0 – 3.0) | 0.05 |
| DDR1 (N=20) | 13.6 | 11.7 | 0.9 (0.4 – 1.9) | 0.82 | 6.2 | 5.5 | 0.9 (0.5 – 1.7) | 0.78 |
| ERBB21 (N=19) | NR | 11.7 | 0.7 (0.3 – 1.6) | 0.36 | 6.9 | 5.8 | 0.6 (0.3 – 1.3) | 0.31 |
| TSC11 (N=15) | NR | 11.7 | 0.4 (0.1 – 1.5) | 0.16 | 6.0 | 5.8 | 0.6 (0.2 – 1.5) | 0.23 |
| TMB high (≥10 Mut/Mb)2 (N=34) | 13.6 | 8.3 | 0.4 (0.2 – 0.9) | 0.02 | 6.0 | 4.8 | 0.7 (0.4 – 1.2) | 0.14 |
| CDKN2A + CDKN2B1 (N=28) | 7.8 | 17.3 | 1.6 (0.9 – 2.9) | 0.11 | 4.4 | 6.0 | 2.0 (1.2 – 3.3) | <0.01 |
| CDKN2B + MTAP1 (N=14) | 7.8 | 11.7 | 1.5 (0.7 – 3.2) | 0.24 | 4.4 | 6.0 | 2.4 (1.3 – 4.4) | <0.01 |
1155 evaluable for OS and 135 evaluable for PFS 2113 evaluable for OS and 98 evaluable for PFS.
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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 450)
DOI
10.1200/JCO.2023.41.6_suppl.450
Abstract #
450
Poster Bd #
C7
Abstract Disclosures
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