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The role of immune checkpoint inhibitors (ICI) as adjuvant treatment in renal cell carcinoma (RCC): A Systematic Review and Meta-Analysis

  • Fernando Sabino Marques Monteiro
    Correspondence
    First and Corresponding Author, Fernando Sabino M. Monteiro, MD, Oncology and Hematology Department, Hospital Santa Lucia, SHLS 716 Cj C, ZIP Code: 70390-700, Brasilia, DF, Brazil
    Affiliations
    Latin American Cooperative Oncology Group – LACOG, Av. Ipiranga 6681, ZIP Code: 90619-900, Porto Alegre, RS, Brazil

    Hospital Santa Lucia, SHLS 716 Cj. C, Zip Code: 70390-700, Brasilia, DF, Brazil

    Hospital Universitário de Brasília, SGAN 605, Zip Code: 70840-901, Brasilia, DF, Brazil
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  • Andrey Soares
    Affiliations
    Latin American Cooperative Oncology Group – LACOG, Av. Ipiranga 6681, ZIP Code: 90619-900, Porto Alegre, RS, Brazil

    Hospital Albert Einstein, Av. Albert Einstein 627, Zip Code: 05652-900, São Paulo, SP, Brazil

    Centro Paulista de Oncologia/Grupo Oncoclínicas, Av. Brg. Faria Lima 4300, Zip Code: 04538-132, São Paulo, SP Brazil
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  • Alessandro Rizzo
    Affiliations
    Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy
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  • Matteo Santoni
    Affiliations
    Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100, Macerata, Italy
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  • Veronica Mollica
    Affiliations
    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy

    Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy
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  • Enrique Grande
    Affiliations
    MD Anderson Cancer Center Madrid, C. de Arturo Soria 270, ZIP Code: 28033, Madrid, Spain
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  • Francesco Massari
    Affiliations
    Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy

    Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy
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Published:January 19, 2023DOI:https://doi.org/10.1016/j.clgc.2023.01.005

      Highlights

      • Adjuvant systemic treatment with sunitinib for patients with renal cell carcinoma (RCC) is controversial
      • Systemic adjuvant treatment with Sunitinib improves disease-free survival, however with considerable toxicity
      • Adjuvant systemic treatment with immune checkpoint inhibitors (ICI) is associated with lower risk of toxicity, however with conflicting clinical benefit
      • This meta-analysis, with the available high-level data of adjuvant systemic treatment with ICI for RCC patients, was not able to demonstrate survival benefit in the overall population.

      Abstract

      Background

      Pembrolizumab, a PD-1 ICI is approved for the adjuvant treatment of post-nephrectomy patients with clear cell RCC in some countries worldwide. However, recent negative data from randomized clinical trials (RCT) with another ICIs makes the benefit of this treatment uncertain.

      Methods

      A systematic review and study-level meta-analysis was performed to evaluate the benefit of disease-free survival (DFS) with adjuvant ICI treatment for patients with localized and/or metastatic resected RCC. Using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to September 15, 2022. The statistical analysis was performed by ProMeta 3 software in intention-to-treat (ITT) population and in predetermined subgroups.

      Results

      Four RCT totalizing 3407 patients were included in this analysis. Systemic immunotherapy was pembrolizumab, atezolizumab, nivolumab and ipilimumab plus nivolumab in 496, 390, 404 and 405 patients, respectively. In the ITT population there was a non-statistically significant DFS benefit with adjuvant ICI (HR: 0.85, 95% CI:0.69-1.04). Regarding the subgroups, there was a DFS benefit for PD-L1 positive (HR: 0.72; 95% CI, 0.55-0.94), intermediate-high risk patients (HR: 0.77; 95% CI, 0.63-0.94), and patients with sarcomatoid component (HR: 0.66; 95% CI:0.43-0.99).

      Conclusion

      This meta-analysis did not demonstrate a statistically significant DFS benefit in overall population, however considering the heterogeneity between the RCTs the use of adjuvant ICI should be individualized.

      Keywords

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