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New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors

Bamias, Aristotelis, Merseburger, Axel, Loriot, Yohann, James, Nicholas, Choy, Ernest ORCID:, Castellano, Daniel, Lopez-Rios, F., Calabrò, Fabio, Kramer, Mario, de Velasco, Guillermo, Zakopoulou, Roubini, Tzannis, Kimon and Sternberg, Cora N. 2023. New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors. Journal for ImmunoTherapy of Cancer 11 , e005977. 10.1136/jitc-2022-005977

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Background: Bellmunt Risk Score, based on Eastern Cooperative Oncology Group (ECOG) performance status (PS), hemoglobin levels and presence of liver metastases, is the most established prognostic algorithm for patients with advanced urothelial cancer (aUC) progressing after platinum-based chemotherapy. Nevertheless, existing algorithms may not be sufficient following the introduction of immunotherapy. Our aim was to develop an improved prognostic model in patients receiving second-line atezolizumab for aUC. Methods: Patients with aUC progressing after cisplatin/carboplatin-based chemotherapy and enrolled in the prospective, single-arm, phase IIIb SAUL study were included in this analysis. Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The development and internal validation of a prognostic model for overall survival (OS) was performed using Cox regression analyses, bootstrapping methods and calibration. Results: In 936 patients, ECOG PS, alkaline phosphatase, hemoglobin, neutrophil-to-lymphocyte ratio, liver metastases, bone metastases and time from last chemotherapy were identified as independent prognostic factors. In a 4-tier model, median OS for patients with 0–1, 2, 3–4 and 5–7 risk factors was 18.6, 10.4, 4.8 and 2.1 months, respectively. Compared with Bellmunt Risk Score, this model provided enhanced prognostic separation, with a c-index of 0.725 vs 0.685 and increment in c-statistic of 0.04 (p<0.001). Inclusion of PD-L1 expression did not improve the model. Conclusions: We developed and internally validated a prognostic model for patients with aUC receiving postplatinum immunotherapy. This model represents an improvement over the Bellmunt algorithm and could aid selection of patients with aUC for second-line immunotherapy. Trial registration number: NCT02928406.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Start Date: 2023-01-10, Type: open-access
Publisher: BMJ Publishing Group
Date of First Compliant Deposit: 18 January 2023
Date of Acceptance: 23 December 2022
Last Modified: 03 May 2023 08:40

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