Re-evaluating Treatments for Advanced Urothelial Carcinoma Using Restricted Mean Survival Time: A Systematic Review and Network Meta-analysis - PubMed

4 days ago

The study re-evaluates treatments for advanced urothelial carcinoma (UC) using restricted mean survival time (RMST) due to potential violations of the proportional hazards (PH) assumption in immune checkpoint inhibitor (ICI) trials.
A systematic review and network meta-analysis (NMA) of 7 phase 2/3 randomized controlled trials (2015-2025) involving 5321 patients was conducted, with individual patient data reconstructed from Kaplan-Meier curves.
PH assumption violations were found in 50% of overall survival (OS) and 60% of progression-free survival comparisons, indicating time-dependent treatment effects not captured by traditional hazard ratios.
ICI monotherapy showed early detriment at 12 months compared to chemotherapy (PD-1 inhibitors: -0.8 months; PD-L1 inhibitors: -0.9 months), which was masked by nonsignificant hazard ratios.
Enfortumab vedotin + pembrolizumab demonstrated the largest RMST benefit (5.7 months at 36 months), though findings are based on a single pivotal trial and require further validation.
The study highlights the value of RMST analysis as a complementary approach for evaluating time-dependent treatment effects in immunotherapy trials, especially where PH assumptions may not hold.
Limitations include sparse network structure and heterogeneous patient eligibility criteria across trials.

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