Photo Credit: Marcin Klapczynski

The following is a summary of “Novel therapeutic regimens in previously untreated metastatic urothelial carcinoma: A systematic review and Bayesian Network Meta-analysis,” published in the August 2024 issue of Urology by Hinojosa-Gonzalez et al.

Historically, metastatic urothelial carcinoma (mUC) has posed significant treatment challenges due to a scarcity of effective therapeutic options. Recently, immune checkpoint inhibitors (ICIs) have emerged as promising alternatives, particularly for patients ineligible for cisplatin-based therapies. Despite this advancement, a comprehensive direct comparison of these ICIs remains absent. This study aims to bridge this gap by employing a Bayesian network meta-analysis to indirectly compare the efficacy of ICIs as first-line treatments for mUC. A systematic review was conducted to gather data from randomized controlled trials evaluating various ICIs in this context. The collected data were analyzed using Review Manager 5.4 for pairwise meta-analysis and subsequently utilized to construct a network in R Studio. The network model was based on 200,000 Markov Chains simulated through Monte Carlo sampling. 

Results are reported as hazard ratios (HR) with 95% credible intervals (CrI). The analysis included six studies encompassing 5,449 patients, of whom 3,255 received either ICI monotherapy or combination therapy. Among these, 3,006 patients had PD-L1 positive tumors and 2,362 had PD-L1 negative tumors. The median overall survival (OS) varied from 12.1 to 31.5 months across studies. Notably, the combination therapy of enfortumab vedotin and pembrolizumab achieved the most substantial reduction in mortality risk (HR 0.47 [95% CrI: 0.38, 0.58]), followed by avelumab monotherapy (HR 0.69 [95% CrI: 0.56, 0.86]). However, this network meta-analysis is limited by variations in study follow-up durations, inconsistent methodologies for assessing PD-L1 positivity, and potential biases stemming from control arms with less favorable survival outcomes. 

The combination of enfortumab vedotin and pembrolizumab was associated with significant improvements in survival and response rates, while avelumab demonstrated considerable single-agent efficacy. These findings offer a crucial framework for guiding clinical decisions and underscore key areas for further research, such as refining biomarkers and exploring innovative combination therapies to enhance antitumor immunity in metastatic urothelial carcinoma.

Source: sciencedirect.com/science/article/abs/pii/S1078143924005441