Comparative Effectiveness of Immune Checkpoint Inhibitors in Patients with Platinum-Refractory Advanced Urothelial Carcinoma
Menée aux Etats-Unis dans un contexte de vie réelle à partir de données portant sur 609 patients atteints d'un carcinome urothélial de stade avancé et réfractaire aux sels de platine, cette étude de cohorte compare l'efficacité, du point de vue de la survie globale, du délai avant le début du traitement de troisième ligne ou avant le décès, de différents inhibiteurs de PD-1/PD-L1
Purpose: Five programmed cell death protein 1 (PD-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. Herein we compared time to initiation of third therapy or death (TTTTD) and overall survival (OS) with different PD-1/L1 inhibitors in patients with platinum-refractory metastatic urothelial carcinoma. Methods: Patient-level data from a real-world de-identified database was extracted. 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 PD-1/L1 inhibitor after disease progression from 8/1/2016 through 5/1/2019. Results: Overall 609 patients were eligible for analysis. Median TTTTD with atezolizumab, nivolumab, and pembrolizumab was 4.2, 5.3, and 4.5 months and median OS was 6.4, 8.0, and 8.3 months, respectively. Matching weighted analyses did not show strong evidence of differences among PD-1/L1 inhibitors in terms of TTTTD and OS. Conclusions: In this large real-world cohort, effectiveness in terms of TTTTD and OS with PD-1/L1 inhibitors in patients with platinum-refractory locally advanced/unresectable or metastatic urothelial carcinoma was similar.
Journal of Urology 2020