Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
A partir d'une revue systématique de la littérature publiée jusqu'en décembre 2023 (14 études, 5 271 patients), cette méta-analyse évalue l'association entre l'expression tumorale de PD-L1, le taux de réponse objective au traitement et la survie globale chez des patients atteints d'un carcinome urothélial de stade métastatique traité par inhibiteurs de point de contrôle immunitaire
Importance : Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1) with response and survival in patients treated with ICIs is still controversial. Objectives : To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs. Data Sources : PubMed, Embase, American Society of Clinical Oncology and European Society for Medical Oncology Meeting Libraries, and Web of Science were searched up to December 10, 2023. Study Selection : Two authors independently screened the studies. Included studies were randomized and nonrandomized clinical trials enrolling patients with mUC receiving ICIs with available overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) data, separated between patients with PD-L1–positive and –negative tumors. Data Extraction and Synthesis : The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Two reviewers independently extracted data. Fixed- or random-effects models were used depending on the heterogeneity among the studies. Main Outcomes and Measures : Primary outcomes were odds ratios (ORs) for ORR and hazard ratios (HRs) for OS, comparing patients with PD-L1–positive tumors and patients with PD-L1–negative tumors. Secondary outcomes were the PFS HR between patients with PD-L1–positive and –negative tumors and OS HR between ICI arms and non-ICI arms of only randomized clinical trials. Results : A total of 14 studies were selected, comprising 5271 patients treated with ICIs (2625 patients had PD-L1–positive tumors). The ORR was 13.8% to 78.6% in patients with PD-L1–positive tumors and 5.1% to 63.2% in patients with PD-L1–negative tumors, with an association between PD-L1 status and ORR favoring patients with PD-L1–positive tumors (OR, 1.94; 95% CI, 1.47-2.56; P < .001). Median OS ranged from 8.4 to 24.1 months in patients with PD-L1–positive tumors and from 6.0 to 19.1 months in patients with PD-L1–negative tumors. The pooled HR showed a significant reduction for patients with PD-L1–positive tumors compared with those with PD-L1–negative tumors in the risk of death (HR, 0.71; 95% CI, 0.57-0.89; P = .003) and risk of progression (HR, 0.55; 95% CI, 0.44-0.69; P < .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response. Conclusions and Relevance : This systematic review and meta-analysis suggests that PD-L1 expression is associated with improved ORR, OS, and PFS for patients with mUC who receive ICIs, but it is unlikely to be useful as a predictive biomarker. Developing predictive biomarkers is essential to select patients most likely to benefit from ICIs and avoid toxic effects and financial burden with these agents.
JAMA Network Open 2024