Abstract
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.
| Original language | English |
|---|---|
| Article number | e005977 |
| Journal | Journal for ImmunoTherapy of Cancer |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 10.01.2023 |
Funding
The authors would like to thank the patients participating in the trial and their families, the investigators, and F Hoffmann-La Roche for providing the clinical trial data from the SAUL study. Editorial support was provided by Katrin Gudmundsdottir, PhD (KG Medical Writing Ltd) funded by the HGUCG. The SAUL trial was sponsored and funded by F. Hoffmann-La Roche, Basel, Switzerland. F Hoffmann-La Roche played a role in the design and conduct of the original study and in the collection, management, analysis, and interpretation of the original study data but had no involvement in the analysis reported in this manuscript. This sub-analysis of the SAUL trial was funded by the Hellenic Genito-Urinary Cancer Group (HGUCG). HGUCG provided support in the preparation of this manuscript but had no involvement in the design of the study or the collection, management, analysis and interpretation of the data.
Research Areas and Centers
- Research Area: Luebeck Integrated Oncology Network (LION)
- Centers: University Cancer Center Schleswig-Holstein (UCCSH)
DFG Research Classification Scheme
- 2.22-14 Hematology, Oncology
- 2.22-23 Reproductive Medicine, Urology
- 2.21-05 Immunology
