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Meta-Analysis
. 2022 Oct;20(5):391-398.
doi: 10.1016/j.clgc.2022.04.008. Epub 2022 Apr 25.

A Systematic Review and Meta-Analysis of the Role of Immune Checkpoint Inhibitors (ICI) as Adjuvant Treatment for Localized High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC)

Fernando Sabino M Monteiro  1 , Andrey Soares  2 , Vinicius Carrera Souza  3 , Rubens Copia Sperandio  4 , Enrique Grande  5 , Matteo Santoni  6 , Andre Poisl Fay  7 , Andre Deeke Sasse  8
Affiliations
Meta-Analysis

A Systematic Review and Meta-Analysis of the Role of Immune Checkpoint Inhibitors (ICI) as Adjuvant Treatment for Localized High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC)

Fernando Sabino M Monteiro et al. Clin Genitourin Cancer. 2022 Oct.

Abstract

Nivolumab, a PD-1 ICI has been recently approved for the adjuvant treatment of high-risk MIUC patients. However, conflicting data from another randomized controlled trial (RCT) with atezolizumab makes the benefit of this treatment uncertain. We performed a systematic review and study-level meta-analysis to evaluate the benefit in terms of disease-free survival (DFS) with ICI adjuvant treatment for patients with high-risk MIUC. Considering the Preferred Reporting Items for Systematic Review statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to October 30, 2021. The statistical analysis was performed by RevMan 5.4 software in intention-to-treat (ITT) population and in predetermined subgroups. Two RCTRCT, with a total of 1518 patients, met the inclusion criteria. Systemic immunotherapy was atezolizumab for 406 patients and nivolumab for 353 patients. In the ITT population there was a nonsignificant benefit with the systemic adjuvant immunotherapy (HR:0.79, 95% CI 0.62-1.00; z = 2.00) but with high heterogeneity (I2 = 65%). Regarding the subgroups, there was no benefit in PD-L1 negative (HR:0.81, 95% CI 0.70-1.00; z = 1.96, I2 = 0%) and in non-neoadjuvant chemotherapy (HR:0.95, 95% CI 0.78-1.15; z = 0.56, I2 = 0%). Adjuvant treatment with ICI to patients with high-risk MIUC reveals a nonsignificant impact in DFS. The lack of clinical benefit was demonstrated in all subgroups. These data reinforce the need for a careful selection of patients before offering this approach in daily practice.

Keywords: Immunotherapy; Localized disease; adjuvant treatment; high-risk urothelial carcinoma; immune check-point inhibitors.

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Conflict of interest statement

Disclosures Fernando Sabino M. Monteiro: Consulting or Advisory Role: Janssen, Astra Zeneca. Speaker's Bureau: Janssen, Ipsen, MSD Oncology, BMS Brazil, Pfizer/EMD Serono. Research Funding: Janssen, MSD Oncology. Travel, Accommodations, Expenses: Janssen, Zodiac. Andrey Soares: Honoraria: Janssen, Pfizer, Bayer, Novartis, AstraZeneca, Astellas Pharma, Pierre Fabre, Merck Serono, Sanofi,Roche, Ipsen, Zodiac. Consulting or Advisory Role: Astellas Pharma, Janssen, Roche, Bayer, Lilly, AstraZeneca, Novartis, MSD, Bristol-Myers Squibb, Zodiac, Amgem, Ipsen, United, Zodiac. Research Funding: Bristol-Myers Squibb (Inst), Astellas (Inst), AstraZeneca (Inst). Travel, Accommodations, Expenses: AstraZeneca,Pfizer, AstellasPharma, Bristol-Myers Squibb, Bayer, Roche, Janssen, Merck Serono, Sanofi, Ipsen, Zodiac. Andre Poisl Fay: Research funding: Janssen, Astellas, Pfizer. Honoraria: Janssen, Astellas, Pfizer, AztraZeneca, Roche, MSD, BMS, Roche. Travel, Accommodations, Expenses: Janssen, IPSEN, MSD, Astellas. Enrique Grande: Honoraria: Adacap, AMGEN, Angelini, Astellas, Astra Zeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, IPSEN, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre Fabre, Pfizer, Roche, Sanofi-Genzyme, Servier, Taiho, and Thermo Fisher Scientific. Research Funding: Pfizer, Astra Zeneca, Astellas, and Lexicon Pharmaceuticals. All other authors do not have relationships to disclose.