Impact of Label Restriction on Checkpoint-Inhibitor Use in Bladder Cancer and Changes in Mortality
Daniel T Vader1, Ravi B Parikh2,3, Haojie Li4
1Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
In 2018, the US Food and Drug Administration (FDA) limited the indication for immune checkpoint inhibitors (ICI) in metastatic bladder cancer to patients with programmed cell death protein ligand-1 (PD-L1)-positive tumors. The impact of the label change on survival outcomes remains unknown. We conducted a controlled interrupted time series analysis using a nationwide electronic health record-derived oncology dataset. We used Cox regression to compare mortality in the post- vs prelabel change periods among affected (initiators of ICI or carboplatin-based chemotherapy) vs unaffected (initiators of cisplatin-based chemotherapy) patients. The use of ICI, carboplatin, and cisplatin was similar pre- and postlabel change, but PD-L1 testing increased postlabel change. In adjusted models, survival did not differ after the FDA label change policy compared with prior to the label change in any of the groups. The FDA label restriction on immunotherapy was associated with increased PD-L1 testing but not with changes in treatment patterns or mortality among patients with metastatic bladder cancer.
Insights
The FDA restricted immunotherapy for metastatic bladder cancer, increasing PD-L1 testing but not impacting survival outcomes or treatment patterns. This study analyzed survival data following the 2018 label change.
Area of Science:
- Oncology
- Immunotherapy
- Health Policy
Background:
- In 2018, the FDA restricted immune checkpoint inhibitors (ICI) for metastatic bladder cancer to PD-L1-positive tumors.
- The effect of this policy change on patient survival was previously unknown.
Purpose of the Study:
- To evaluate the impact of the FDA's 2018 label change for ICI on survival outcomes in metastatic bladder cancer.
- To assess changes in treatment patterns and PD-L1 testing following the policy update.
Main Methods:
- A controlled interrupted time series analysis was performed using a nationwide electronic health record-derived oncology dataset.
- Cox regression models compared mortality rates before and after the label change.
- Patients were stratified based on treatment initiation: ICI or carboplatin (affected) vs. cisplatin (unaffected).
Main Results:
- Programmed cell death protein ligand-1 (PD-L1) testing significantly increased after the FDA label change.
- No significant differences in survival outcomes were observed post-label change compared to the pre-label change period across all patient groups.
- Treatment patterns, including the use of ICI, carboplatin, and cisplatin, remained consistent before and after the policy change.
Conclusions:
- The FDA's 2018 restriction on immunotherapy for metastatic bladder cancer led to increased PD-L1 testing.
- The policy change did not alter treatment selection or improve/worsen survival outcomes for patients with metastatic bladder cancer.
- This suggests the label restriction had minimal impact on clinical practice and patient mortality.
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