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Comparative Effectiveness of Immune Checkpoint Inhibitors in Patients with Platinum Refractory Advanced Urothelial
Umang Swami1, Benjamin Haaland1,2, Adam Kessel1
1Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
Purpose:
Five programmed cell death protein 1 or its ligand (L1) inhibitors are approved for treatment of platinum refractory, locally advanced/unresectable or metastatic urothelial carcinoma. However, their comparative effectiveness is unknown. We compared time to initiation of third therapy or death, and overall survival with different programmed cell death protein 1/L1 inhibitors in patients with platinum refractory metastatic urothelial carcinoma.
Materials And Methods:
Patient-level data were extracted from a real-world de-identified database. Comparative effectiveness was inferred via Cox proportional hazards model, weighted by matching weights. Each patient's propensity for each treatment was modeled via random forest, based on potential drivers of treatment selection. A propensity score for each therapy was used to calculate a matching weight, targeting the same estimand as 1:1 matching of treatment groups with balance among potential confounders. Eligibility criteria included diagnosis of metastatic urothelial carcinoma, receipt of first line treatment with a platinum based chemotherapy, followed by initiation of single agent programmed cell death protein 1/L1 inhibitor after disease progression from August 1, 2016 through May 1, 2019.
Results:
Overall, 609 patients were eligible for analysis. Median time to initiation of third therapy or death with atezolizumab, nivolumab and pembrolizumab was 4.2, 5.3 and 4.5 months, respectively, and median overall survival was 6.4, 8.0 and 8.3 months, respectively. Matching weighted analyses did not show strong evidence of differences among programmed cell death protein 1/L1 inhibitors in terms of time to initiation of third therapy or death and overall survival.
Conclusions:
In this large real-world cohort, effectiveness in terms of time to initiation of third therapy or death and overall survival with programmed cell death protein 1/L1 inhibitors in patients with platinum refractory locally advanced/unresectable or metastatic urothelial carcinoma was similar.
Insights
In patients with advanced urothelial carcinoma, programmed cell death protein 1 (PD-1) or ligand 1 (L1) inhibitors showed similar effectiveness for time to third therapy or death and overall survival. These findings suggest comparable outcomes across different PD-1/L1 inhibitors in this patient population.
Area of Science:
- Oncology
- Immunotherapy
- Urothelial Carcinoma
Background:
- Five programmed cell death protein 1 (PD-1) or its ligand 1 (L1) inhibitors are approved for platinum-refractory urothelial carcinoma.
- Comparative effectiveness of these PD-1/L1 inhibitors is not well-established in real-world settings.
Purpose of the Study:
- To compare the effectiveness of different PD-1/L1 inhibitors in patients with platinum-refractory metastatic urothelial carcinoma.
- To evaluate time to initiation of third therapy or death and overall survival.
- To analyze real-world patient data for comparative effectiveness.
Main Methods:
- Retrospective analysis of a real-world, de-identified patient database.
- Used Cox proportional hazards model with matching weights for comparative effectiveness.
- Propensity for each treatment modeled using random forest to balance confounders.
Main Results:
- Analysis included 609 eligible patients with metastatic urothelial carcinoma.
- Median time to third therapy or death: atezolizumab (4.2 months), nivolumab (5.3 months), pembrolizumab (4.5 months).
- Median overall survival: atezolizumab (6.4 months), nivolumab (8.0 months), pembrolizumab (8.3 months).
Conclusions:
- Matching weighted analyses indicated no significant differences in effectiveness among PD-1/L1 inhibitors.
- Effectiveness regarding time to third therapy or death and overall survival was similar across PD-1/L1 inhibitors.
- Real-world data suggest comparable outcomes for PD-1/L1 inhibitors in platinum-refractory urothelial carcinoma.
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