Ali Raza Khaki1, Ang Li2, Leonidas N Diamantopoulos1, Mehmet A Bilen3, Victor Santos4, John Esther4, Rafael Morales-Barrera5, Michael Devitt6, Ariel Nelson7, Christopher J Hoimes7, Evan Shreck8,9, Hussein Assi10, Benjamin A Gartrell8,9, Alex Sankin8,9, Alejo Rodriguez-Vida11, Mark Lythgoe12, David J Pinato12, Alexandra Drakaki13, Monika Joshi14, Pedro Isaacsson Velho15, Noah Hahn15, Sandy Liu13, Lucia Alonso Buznego16, Ignacio Duran16, Marcus Moses17, Jayanshu Jain18, Jure Murgic19, Praneeth Baratam20, Pedro Barata17, Abhishek Tripathi10, Yousef Zakharia21, Matthew D Galsky22, Guru Sonpavde23, Evan Y Yu1, Veena Shankaran1, Gary H Lyman1,24, Petros Grivas1. 1. Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington. 2. Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington. 3. Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia. 4. Department of Medicine, University of Utah, Salt Lake City, Utah. 5. Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain. 6. Division of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia. 7. Division of Hematology/Oncology, Department of Medicine, Case Comprehensive Cancer Center, Cleveland, Ohio. 8. Department of Medical Oncology, Montefiore Medical Center, Bronx, New York. 9. Department of Urology, Montefiore Medical Center, Bronx, New York. 10. Section of Hematology Oncology, Department of Medicine, University of Oklahoma Stephenson Cancer Center, Oklahoma City, Oklahoma. 11. Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain. 12. Department of Surgery and Cancer, Imperial College London, London, United Kingdom. 13. Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 14. Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, Pennsylvania. 15. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. 16. Marques de Valdecilla University Hospital, Instituto de Investigacion Sanitaria Valdecilla, Santander, Spain. 17. Department of Medicine and Oncology, Tulane University, New Orleans, Louisiana. 18. Department of Medicine, University of Iowa, Iowa City, Iowa. 19. Department of Oncology and Nuclear Medicine, University Hospital Center, Sisters of Charity Zagreb School of Medicine, Zagreb, Croatia. 20. College of Medicine, Drexel University, Philadelphia, Pennsylvania. 21. Division of Oncology, Department of Medicine, University of Iowa, Iowa City, Iowa. 22. Division of Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. 23. Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 24. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0-1) would correlate with shorter overall survival (OS) in patients receiving ICIs. METHODS: In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013-2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested. RESULTS: Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04). CONCLUSIONS: Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first-line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.
BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0-1) would correlate with shorter overall survival (OS) in patients receiving ICIs. METHODS: In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013-2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested. RESULTS: Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04). CONCLUSIONS: Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first-line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.
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