Meeting
2022 ASCO Genitourinary Cancers Symposium
Clinical outcomes in advanced urothelial cancer (UC) patients who experienced immune-related adverse events (irAEs) after immune checkpoint inhibitor monotherapy (ICI).
Authors
Gregory E. Sanda
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA
Gregory E. Sanda , Julie M. Shabto , Subir Goyal , Yuan Liu , Dylan J. Martini , Bassel Nazha , Jacqueline T Brown , Lauren Beth Yantorni , Greta Russler , Sarah Caulfield , Shreyas S. Joshi , Vikram M. Narayan , Haydn Kissick , Kenneth Ogan , Viraj A. Master , Bradley Curtis Carthon , Omer Kucuk , Mehmet Asim Bilen
Organizations
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, Winship Cancer Institute and Rollins School of Public Health at Emory University, Atlanta, GA, Departments of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, Dana-Farber Cancer Institute, Boston, MA, Emory University Department of Hematology and Medical Oncology, Atlanta, GA, Winship Cancer Institute of Emory University, Atlanta, GA, Department of Urology, Emory University School of Medicine, Atlanta, GA, Emory University School of Medicine Winship Cancer Institute, Atlanta, GA, Emory University Hospital Midtown, Atlanta, GA
Research Funding
No funding received
Background: Immune checkpoint inhibitors (ICIs) continue to demonstrate promise in treatment of advanced urothelial carcinoma (UC). Some patients undergoing ICIs experience immune related adverse events (irAEs) and may serve as a marker of response. We investigated the relationship between irAEs and clinical outcomes in UC patients treated with ICIs. Methods: A retrospective study of 70 UC patients treated with ICI monotherapies at Winship Cancer Institute from 2015-2020 was done. Overall survival (OS) and progression-free survival (PFS), defined as time from ICI initiation to death and clinical or radiographic progression, respectively as well as clinical benefit (CB), defined as best radiographic response of complete response, partial response, or stable disease for ≥ 6 months per RECIST v1.1, were used to measure clinical outcomes. Cox proportional hazards and multivariable analyses (MVA) were used to model associations with OS and PFS. Results: Most patients were male (70%) with a median age of 68.7 years (28.0-91.0). Most patients (95%) had urothelial carcinoma and most (81%) received at least 1 prior treatment. One third of patients had ECOG PS greater than or equal to 2. Of patients that experienced an irAE (35%), the most common were dermatologic (12.9%) and arthralgia (0.5%). In addition to significantly longer treatment duration, irAE patients had significantly increased OS (HR:0.38, 95% CI:0.18-0.79, p=0.009), significantly longer PFS (HR:0.27, 95% CI:0.14-0.53, p < 0.001), and significantly greater CB (OR:4.20, 95% CI:1.35-13.06, p=0.013). Patients who experienced dermatologic irAEs had significantly increased OS, PFS, and CB (Table). Conclusions: Our results demonstrate that UC patients undergoing ICI therapy who experience irAEs, especially dermatologic irAEs, had improved clinical outcomes. This suggests that irAEs may serve as a clinical biomarker of advantageous response in patients receiving ICI. Future prospective studies are needed for validation.
| Variable | Total weeks on treatment | OS | PFS | CB | ||||
|---|---|---|---|---|---|---|---|---|
| B | p-value | HR (CI) | p-value | HR (CI) | p-value | OR (CI) | p-value | |
| irAE (n=25) | 24.74 (9.67-39.81) | 0.002** | 0.38 (0.18-0.79) | 0.009** | 0.27 (0.14-0.53) | <0.001** | 4.2 (1.35-13.06) | 0.013** |
| Median OS(CI): NR (9.9, NR) | Median PFS (CI): 8.5 (3.3, NR) | CB rate: 52% | ||||||
| No irAE (n=45) | 1 | 1 | 1 | 1 | ||||
| Median OS (CI): 7.1 (2.4, 11.7) | Median PFS (CI): 2.2 (1.7, 3.2) | CB rate: 23% | ||||||
| Derm. irAE (n= 9) | 34.12 (12.42-55.82) | 0.003** | 0.23(0.07-0.78) | 0.019** | 0.18 (0.06-0.53) | 0.002** | 7.68 (1.51-38.93) | 0.014** |
| Median OS (CI): NR (5.5, NR) | Median PFS (CI): 33.3 (2.8, NR) | CB rate: 67% | ||||||
| No derm. irAE (n=61) | 1 | 1 | 1 | 1 | ||||
| Median OS(CI): 9.2 (5.8, 12.4) | Median PFS (CI) 2.6 (2.2, 3.8) | CB rate: 29% | ||||||
*MVA were build using the backward selection method at alpha level of 0.1. **Statistical significance at alpha < 0.05.
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session B: Urothelial Carcinoma
Track
Urothelial Carcinoma
Sub Track
Translational Research, Tumor Biology, Biomarkers, and Pathology
Citation
J Clin Oncol 40, 2022 (suppl 6; abstr 544)
DOI
10.1200/JCO.2022.40.6_suppl.544
Abstract #
544
Poster Bd #
J2
Abstract Disclosures
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