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- Title
Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.
- Authors
Maiorano, Brigida Anna; Di Maio, Massimo; Cerbone, Linda; Maiello, Evaristo; Procopio, Giuseppe; Roviello, Giandomenico
- Abstract
Key Points: Question: Is programmed death ligand 1 (PD-L1) associated with improved outcomes among patients with urothelial carcinoma treated with immune checkpoint inhibitors (ICIs)? Findings: In this systematic review and meta-analysis of 14 phase 1 to 3 studies, an association emerged between PD-L1 status and overall response rate, favoring patients with PD-L1–positive tumors. There was a significant reduction in the risk of disease progression and death for patients with PD-L1–positive tumors compared with patients with PD-L1–negative tumors. Meaning: This study suggests that PD-L1–positive tumors are associataed with improved prognosis among patients with metastatic urothelial carcinoma who recieve ICIs, but PD-L1 is not likely to be a predictive biomarker of ICI response. 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. This systematic review and meta-analysis evaluates the association of programmed death ligand 1 (PD-L1) with overall response rate and overall survival among patients with metastatic urothelial carcinoma treated with immune checkpoint inhibitors.
- Subjects
CANCER chemotherapy; CANCER prognosis; MEDICAL information storage &; retrieval systems; URINARY organs; PROGRAMMED death-ligand 1; META-analysis; TREATMENT effectiveness; DESCRIPTIVE statistics; IMMUNE checkpoint inhibitors; METASTASIS; SYSTEMATIC reviews; MEDLINE; ODDS ratio; ONLINE information services; PROGRESSION-free survival; COMPARATIVE studies; CONFIDENCE intervals; OVERALL survival
- Publication
JAMA Network Open, 2024, Vol 7, Issue 3, pe241215
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.1215