Natalie J Miller1, Ali Raza Khaki1, Leonidas N Diamantopoulos1, Mehmet A Bilen2, Victor Santos3, Neeraj Agarwal3, Rafael Morales-Barrera4, Michael Devitt5, Ariel Nelson6, Christopher J Hoimes6, Evan Shreck7, Hussein Assi8, Benjamin A Gartrell7, Alex Sankin7, Alejo Rodriguez-Vida9, Mark Lythgoe10, David J Pinato10, Alexandra Drakaki11, Monika Joshi12, Pedro Isaacsson Velho13, Noah Hahn13, Sandy Liu11, Lucia Alonso Buznego14, Ignacio Duran14, Marcus Moses15, Jayanshu Jain16, Jure Murgic17, Pedro Barata15, Abhishek Tripathi8, Yousef Zakharia18, Matthew D Galsky19, Guru Sonpavde20, Evan Y Yu1, Gary H Lyman1,21, Petros Grivas1. 1. Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington. 2. Winship Cancer Institute of Emory University, Atlanta, Georgia. 3. Department of Medicine, University of Utah, Salt Lake City, Utah. 4. Vall d´Hebron Institute of Oncology, Vall d´Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. 5. Division of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia. 6. Division of Hematology/Oncology, Department of Medicine, Case Comprehensive Cancer Center, Cleveland, Ohio. 7. Departments of Medical Oncology and Urology, Montefiore Medical Center, Bronx, New York. 8. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. 9. Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain. 10. Division of Medicine, Imperial College London, London, United Kingdom. 11. Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California. 12. Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, Pennsylvania. 13. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. 14. Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain. 15. Department of Medicine and Oncology, Tulane University, New Orleans, Louisiana. 16. Department of Medicine, University of Iowa, Iowa City,Iowa. 17. Department of Oncology and Nuclear Medicine, University Hospital Center Sisters of Charity Zagreb School of Medicine, Zagreb, Croatia. 18. Division of Oncology, Department of Medicine, University of Iowa, Iowa City, Iowa. 19. Division of Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. 20. Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 21. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Abstract
PURPOSE: Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma. MATERIALS AND METHODS: We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards. RESULTS: Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09). CONCLUSIONS: Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.
PURPOSE: Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma. MATERIALS AND METHODS: We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards. RESULTS: Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09). CONCLUSIONS: Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.
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