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Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis
T. Yanagisawa, K. Mori, A. Matsukawa, T. Kawada, S. Katayama, E. Laukhtina, P. Rajwa, F. Quhal, B. Pradere, W. Fukuokaya, K. Iwatani, L. Afferi, G. Marcq, LS. Mertens, A. Gallioli, KH. Tully, J. Caño-Velasco, JD. Subiela, Y. Abu-Ghanem, E....
Language English Country France
Document type Journal Article, Systematic Review, Meta-Analysis
- MeSH
- Chemotherapy, Adjuvant methods MeSH
- Immune Checkpoint Inhibitors * therapeutic use pharmacology MeSH
- Neoplasm Invasiveness MeSH
- Carcinoma, Transitional Cell drug therapy pathology MeSH
- Humans MeSH
- Urinary Bladder Neoplasms drug therapy pathology MeSH
- Network Meta-Analysis as Topic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Systematic Review MeSH
CONTEXT: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. OBJECTIVE: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. EVIDENCE ACQUISITION: In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. EVIDENCE SYNTHESIS: Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. CONCLUSIONS: Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.
2nd Department of Urology Centre of Postgraduate Medical Education Warsaw Poland
Department of Minimally Invasive and Robotic Urology Wrocław Medical University Wrocław Poland
Department of Surgery S H Ho Urology Centre The Chinese University of Hong Kong Hong Kong China
Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Urology Claude Huriez Hospital CHU Lille 59000 Lille France
Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Department of Urology Fundació Puigvert Autonomous University of Barcelona 08193 Barcelona Spain
Department of Urology Gregorio Marañón University Hospital 28007 Madrid Spain
Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia
Department of Urology La Croix Du Sud Hospital Quint Fonsegrives France
Department of Urology Luzerner Kantonsspital 6000 Luzern Switzerland
Department of Urology San Raffaele Hospital and Scientific Institute Milan Italy
Department of Urology University of Texas Southwestern Medical Center Dallas TX USA
Department of Urology Weill Cornell Medical College New York NY USA
Division of Urology Department of Special Surgery The University of Jordan Amman Jordan
Division of Urology Geneva University Hospitals Geneva Switzerland
Institute for Urology and Reproductive Health Sechenov University Moscow Russia
Karl Landsteiner Institute of Urology and Andrology Vienna Austria
The Specialist Centre for Kidney Cancer Royal Free Hospital London UK
References provided by Crossref.org
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- $a Yanagisawa, Takafumi $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. t.yanagisawa.jikei@gmail.com $u Department of Urology, The Jikei University School of Medicine, 3-19-18 Nishi-shimbashi, Minato-ku, Tokyo, 105-8471, Japan. t.yanagisawa.jikei@gmail.com
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- $a CONTEXT: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. OBJECTIVE: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. EVIDENCE ACQUISITION: In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. EVIDENCE SYNTHESIS: Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. CONCLUSIONS: Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.
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