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Targeted Oncology
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13-11-2024 | Checkpoint Inhibitors | Systematic Review

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis

Authors: Takafumi Yanagisawa, Keiichiro Mori, Akihiro Matsukawa, Tatsushi Kawada, Satoshi Katayama, Ekaterina Laukhtina, Pawel Rajwa, Fahad Quhal, Benjamin Pradere, Wataru Fukuokaya, Kosuke Iwatani, Luca Afferi, Gautier Marcq, Laura S. Mertens, Andrea Gallioli, Karl H. Tully, Jorge Caño-Velasco, José Daniel Subiela, Yasmin Abu-Ghanem, Elisabeth Grobet-Jeandin, Francesco Del Giudice, Renate Pichler, Jeremy Yuen-Chun Teoh, Marco Moschini, Wojciech Krajewski, Jun Miki, Shahrokh F. Shariat, Takahiro Kimura, European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU)

Published in: Targeted Oncology | Issue 1/2025

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Abstract

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.
Appendix
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Metadata
Title
Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis
Authors
Takafumi Yanagisawa
Keiichiro Mori
Akihiro Matsukawa
Tatsushi Kawada
Satoshi Katayama
Ekaterina Laukhtina
Pawel Rajwa
Fahad Quhal
Benjamin Pradere
Wataru Fukuokaya
Kosuke Iwatani
Luca Afferi
Gautier Marcq
Laura S. Mertens
Andrea Gallioli
Karl H. Tully
Jorge Caño-Velasco
José Daniel Subiela
Yasmin Abu-Ghanem
Elisabeth Grobet-Jeandin
Francesco Del Giudice
Renate Pichler
Jeremy Yuen-Chun Teoh
Marco Moschini
Wojciech Krajewski
Jun Miki
Shahrokh F. Shariat
Takahiro Kimura
European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU)
Publication date
13-11-2024
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 1/2025
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-024-01114-4

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