While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1).
We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study.
Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study.
We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated.
Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation.
We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued.
With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival.
European urology oncology. 2021 Jan 07 [Epub ahead of print]
Ali Raza Khaki, Ang Li, Leonidas N Diamantopoulos, Natalie J Miller, Lucia Carril-Ajuria, Daniel Castellano, Ivan De Kouchkovsky, Vadim Koshkin, Joseph Park, Ajjai Alva, Mehmet A Bilen, Tyler Stewart, Victor Santos, Neeraj Agarwal, Jayanshu Jain, Yousef Zakharia, Rafael Morales-Barrera, Michael Devitt, Ariel Nelson, Christopher J Hoimes, Evan Shreck, Benjamin A Gartrell, Alex Sankin, Abhishek Tripathi, Roubini Zakopoulou, Aristotelis Bamias, Alejo Rodriguez-Vida, Alexandra Drakaki, Sandy Liu, Vivek Kumar, Mark P Lythgoe, David J Pinato, Jure Murgic, Ana Fröbe, Monika Joshi, Pedro Isaacsson Velho, Noah Hahn, Lucia Alonso Buznego, Ignacio Duran, Marcus Moses, Pedro Barata, Matthew D Galsky, Guru Sonpavde, Evan Y Yu, Veena Shankaran, Gary H Lyman, Petros Grivas
Division of Medical Oncology, Department of Medicine, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA., Section of Hematology/Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA., Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Department of Medicine, University of Washington, Seattle, WA, USA., Hospital Universitario 12 de Octubre, Madrid, Spain., Division of Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA., Winship Cancer Institute of Emory University, Atlanta, GA, USA., Division of Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT, USA., Department of Medicine, University of Iowa, Iowa City, IA, USA., Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA, USA., Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Division of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA., Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH, USA; Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA., Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH, USA; Division of Medical Oncology, Duke University, Durham, NC, USA., Departments of Medical Oncology and Urology, Montefiore Medical Center, Bronx, NY, USA., Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., 2nd Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain., Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Department of Surgery and Cancer, Imperial College London, London, UK., Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, School of Dental Medicine, Zagreb, Croatia., Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, PA, USA., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain., Department of Medicine, Section of Hematology/Oncology, Tulane University, New Orleans, LA, USA., Division of Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Division of Medical Oncology, Department of Medicine, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA. Electronic address: .