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01-02-2025 | Metastasis | Review

Metastatic sites and clinical outcomes in renal cell carcinoma patients receiving immune-based combinations: the MOUSEION-08 study

Authors: Alessandro Rizzo, Fernando Sabino Marques Monteiro, Veronica Mollica, Oronzo Brunetti, Elsa Vitale, Angela Monica Sciacovelli, Andrey Soares, Francesco Massari, Matteo Santoni

Published in: Clinical & Experimental Metastasis | Issue 1/2025

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Abstract

Immune-based combinations have significantly improved the treatment of metastatic renal cell carcinoma (mRCC); however, immunotherapy has reported varying degrees of efficacy across different metastatic sites, with liver and bone metastases traditionally considered more challenging to treat. In MOUSEION-08 study, we aimed to investigate the association between lung, liver, and bone metastases and clinical outcomes such as Overall Survival (OS) and Progression– Free Survival (PFS) in mRCC patients receiving immune-based combinations. The present systematic review and study-level meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). PFS and OS were measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). The protocol was registered with PROSPERO, Registration number: CRD42024581488. Our search resulted in the identification of 2364 potentially relevant reports, which were subsequently restricted to three. The pooled HRs for OS and PFS in patients with lung metastases receiving immune-based combinations versus sunitinib were 0.61 (95% CI, 0.51–0.72) and 0.47 (95% CI, 0.38–0.59), respectively. In patients with liver metastases, the pooled HRs for OS and PFS were 0.56 (95% CI, 0.42–0.75) and 0.48 (95% CI, 0.34–0.67), while the pooled HRs for OS and PFS in patients with bone metastases were 0.64 (95% CI, 0.49–0.84) and 0.36 (95% CI, 0.27–0.49), respectively. According to our findings, the analyses reported similar HRs for OS and PFS, something that further underlines the role of immune-based combinations in this setting, regardless of metastatic sites, such as lung, liver, and bone metastases. Ongoing research and clinical trials are destined to refine and improve immunotherapeutic strategies for mRCC, aiming to enhance efficacy across all metastatic sites and to define predictive biomarkers.
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Literature
1.
go back to reference Motzer RJ, Tannir NM, McDermott DF, Frontera OA, Melichar B, Choueiri TK et al (2018) Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med Motzer RJ, Tannir NM, McDermott DF, Frontera OA, Melichar B, Choueiri TK et al (2018) Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med
2.
go back to reference Quhal F, Mori K, Bruchbacher A, Resch I, Mostafaei H, Pradere B, Schuettfort VM, Laukhtina E, Egawa S, Fajkovic H, Remzi M, Shariat SF, Schmidinger M (2021) First-line immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network Meta-analysis. Eur Urol Oncol 4(5):755–765. https://doi.org/10.1016/j.euo.2021.03.001Epub 2021 Mar 20. PMID: 33757737CrossRefPubMed Quhal F, Mori K, Bruchbacher A, Resch I, Mostafaei H, Pradere B, Schuettfort VM, Laukhtina E, Egawa S, Fajkovic H, Remzi M, Shariat SF, Schmidinger M (2021) First-line immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network Meta-analysis. Eur Urol Oncol 4(5):755–765. https://​doi.​org/​10.​1016/​j.​euo.​2021.​03.​001Epub 2021 Mar 20. PMID: 33757737CrossRefPubMed
3.
go back to reference Dudani S, de Velasco G, Wells JC, Gan CL, Donskov F, Porta C, Fraccon A, Pasini F, Lee JL, Hansen A, Bjarnason GA, Beuselinck B, Pal SK, Yuasa T, Kroeger N, Kanesvaran R, Reaume MN, Canil C, Choueiri TK, Heng DYC (2021) Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association with Survival. JAMA Netw Open 4(1):e2021869. https://doi.org/10.1001/jamanetworkopen.2020.21869. PMID: 33475752; PMCID: PMC7821027CrossRefPubMedPubMedCentral Dudani S, de Velasco G, Wells JC, Gan CL, Donskov F, Porta C, Fraccon A, Pasini F, Lee JL, Hansen A, Bjarnason GA, Beuselinck B, Pal SK, Yuasa T, Kroeger N, Kanesvaran R, Reaume MN, Canil C, Choueiri TK, Heng DYC (2021) Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association with Survival. JAMA Netw Open 4(1):e2021869. https://​doi.​org/​10.​1001/​jamanetworkopen.​2020.​21869. PMID: 33475752; PMCID: PMC7821027CrossRefPubMedPubMedCentral
4.
go back to reference Massari F, Di Nunno V, Guida A, Costa Silva CA, Derosa L, Mollica V, Colomba E, Brandi G, Albiges L (2021) Addition of primary metastatic site on bone, brain, and liver to IMDC Criteria in patients with metastatic renal cell carcinoma: a validation study. Clin Genitourin Cancer 19(1):32–40 Epub 2020 Jun 27. PMID: 32694008CrossRefPubMed Massari F, Di Nunno V, Guida A, Costa Silva CA, Derosa L, Mollica V, Colomba E, Brandi G, Albiges L (2021) Addition of primary metastatic site on bone, brain, and liver to IMDC Criteria in patients with metastatic renal cell carcinoma: a validation study. Clin Genitourin Cancer 19(1):32–40 Epub 2020 Jun 27. PMID: 32694008CrossRefPubMed
6.
go back to reference Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P, Menon M, Montorsi F, Karakiewicz PI (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23(4):973–980. https://doi.org/10.1093/annonc/mdr362Epub 2011 Sep 2. PMID: 21890909CrossRefPubMed Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P, Menon M, Montorsi F, Karakiewicz PI (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23(4):973–980. https://​doi.​org/​10.​1093/​annonc/​mdr362Epub 2011 Sep 2. PMID: 21890909CrossRefPubMed
9.
10.
go back to reference Rassy E, Flippot R, Albiges L (2020) Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma. Ther Adv Med Oncol 12:1758835920907504CrossRefPubMedPubMedCentral Rassy E, Flippot R, Albiges L (2020) Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma. Ther Adv Med Oncol 12:1758835920907504CrossRefPubMedPubMedCentral
11.
go back to reference Albiges L, Powles T, Staehler M et al (2019) Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint inhibition is the New Backbone in First-line treatment of metastatic clear-cell renal cell carcinoma. Eur Urol 76:151–156CrossRefPubMed Albiges L, Powles T, Staehler M et al (2019) Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint inhibition is the New Backbone in First-line treatment of metastatic clear-cell renal cell carcinoma. Eur Urol 76:151–156CrossRefPubMed
12.
go back to reference Powles T, ESMO Guidelines Committee (2021) Electronic address: clinicalguidelines@esmo.org. Recent eUpdate to the ESMO Clinical Practice guidelines on renal cell carcinoma on cabozantinib and nivolumab for first-line clear cell renal cancer: renal cell carcinoma: ESMO Clinical Practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 32:422–423CrossRefPubMed Powles T, ESMO Guidelines Committee (2021) Electronic address: clinicalguidelines@esmo.org. Recent eUpdate to the ESMO Clinical Practice guidelines on renal cell carcinoma on cabozantinib and nivolumab for first-line clear cell renal cancer: renal cell carcinoma: ESMO Clinical Practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 32:422–423CrossRefPubMed
13.
go back to reference Chau V, Bilusic M (2020) Pembrolizumab in Combination with Axitinib as First-Line treatment for patients with renal cell carcinoma (RCC): evidence to date. Cancer Manag Res 12:7321–7330CrossRefPubMedPubMedCentral Chau V, Bilusic M (2020) Pembrolizumab in Combination with Axitinib as First-Line treatment for patients with renal cell carcinoma (RCC): evidence to date. Cancer Manag Res 12:7321–7330CrossRefPubMedPubMedCentral
14.
go back to reference Schmidinger M, Resch I, Fajkovic H, Remzi M, Shariat SF, Bedke J (2021) Dual immune check point blockade or immune check point-tyrosine kinase inhibitor combination: as a first-line treatment in metastatic renal cell carcinoma? Curr Opin Urol 31:270–275CrossRefPubMed Schmidinger M, Resch I, Fajkovic H, Remzi M, Shariat SF, Bedke J (2021) Dual immune check point blockade or immune check point-tyrosine kinase inhibitor combination: as a first-line treatment in metastatic renal cell carcinoma? Curr Opin Urol 31:270–275CrossRefPubMed
15.
go back to reference Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK, CLEAR Trial Investigators (2021) Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med 384(14):1289–1300. https://doi.org/10.1056/NEJMoa2035716Epub 2021 Feb 13. PMID: 33616314CrossRefPubMed Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK, CLEAR Trial Investigators (2021) Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med 384(14):1289–1300. https://​doi.​org/​10.​1056/​NEJMoa2035716Epub 2021 Feb 13. PMID: 33616314CrossRefPubMed
16.
go back to reference Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, Suárez C, Hamzaj A, Porta C, Hocking CM, Kessler ER, Gurney H, Tomita Y, Bedke J, Zhang J, Simsek B, Scheffold C, Apolo AB, Choueiri TK (2022) Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol.;23(7):888–898. https://doi.org/10.1016/S1470-2045(22)00290-X. Epub 2022 Jun 7. Erratum in: Lancet Oncol. 2022;23(7):e319. https://doi.org/10.1016/S1470-2045(22)00346-110.1016/S1470-2045(22)00346-1. Erratum in: Lancet Oncol. 2022;23(9):e404. https://doi.org/10.1016/S1470-2045(22)00511-3. PMID: 35688173; PMCID: PMC10305087 Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, Suárez C, Hamzaj A, Porta C, Hocking CM, Kessler ER, Gurney H, Tomita Y, Bedke J, Zhang J, Simsek B, Scheffold C, Apolo AB, Choueiri TK (2022) Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol.;23(7):888–898. https://​doi.​org/​10.​1016/​S1470-2045(22)00290-X. Epub 2022 Jun 7. Erratum in: Lancet Oncol. 2022;23(7):e319. https://​doi.​org/​10.​1016/​S1470-2045(22)00346-110.1016/S1470-2045(22)00346-1. Erratum in: Lancet Oncol. 2022;23(9):e404. https://​doi.​org/​10.​1016/​S1470-2045(22)00511-3. PMID: 35688173; PMCID: PMC10305087
17.
go back to reference Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthélémy P, Porta C, Powles T, Donskov F, George S, Kollmannsberger CK, Gurney H, Grimm MO, Tomita Y, Castellano D, Rini BI, Choueiri TK, Saggi SS, McHenry MB, Motzer RJ (2020) Nivolumab plus Ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open 5(6):e001079. https://doi.org/10.1136/esmoopen-2020-001079. PMID: 33246931; PMCID: PMC7703447CrossRefPubMedPubMedCentral Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthélémy P, Porta C, Powles T, Donskov F, George S, Kollmannsberger CK, Gurney H, Grimm MO, Tomita Y, Castellano D, Rini BI, Choueiri TK, Saggi SS, McHenry MB, Motzer RJ (2020) Nivolumab plus Ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open 5(6):e001079. https://​doi.​org/​10.​1136/​esmoopen-2020-001079. PMID: 33246931; PMCID: PMC7703447CrossRefPubMedPubMedCentral
20.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefPubMedPubMedCentral Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefPubMedPubMedCentral
21.
go back to reference Higgins JPT, Thomas J, Chandler J et al (2019) Cochrane hand-book for systematic reviews of interventions, 2nd edn. Wiley, Chichester (UK)CrossRef Higgins JPT, Thomas J, Chandler J et al (2019) Cochrane hand-book for systematic reviews of interventions, 2nd edn. Wiley, Chichester (UK)CrossRef
22.
go back to reference Higgins JP, Altman DG, Gøtzsche PC, Cochrane Bias Methods Group; Cochrane Statistical Methods Group et al (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentral Higgins JP, Altman DG, Gøtzsche PC, Cochrane Bias Methods Group; Cochrane Statistical Methods Group et al (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928CrossRefPubMedPubMedCentral
27.
go back to reference Escudier B, Powles T, Motzer RJ, Olencki T, Arén Frontera O, Oudard S, Rolland F,Tomczak P, Castellano D, Appleman LJ, Drabkin H, Vaena D, Milwee S, Youkstetter J,Lougheed JC, Bracarda S, Choueiri TK. Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial. J Clin Oncol. 2018;36(8):765–772. https://doi.org/10.1200/JCO.2017.74.7352. Epub 2018 Jan 8. PMID: 29309249; PMCID: PMC6804840. Escudier B, Powles T, Motzer RJ, Olencki T, Arén Frontera O, Oudard S, Rolland F,Tomczak P, Castellano D, Appleman LJ, Drabkin H, Vaena D, Milwee S, Youkstetter J,Lougheed JC, Bracarda S, Choueiri TK. Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial. J Clin Oncol. 2018;36(8):765–772. https://​doi.​org/​10.​1200/​JCO.​2017.​74.​7352. Epub 2018 Jan 8. PMID: 29309249; PMCID: PMC6804840.
28.
go back to reference Mazurec K, Trzeszcz M, Mazurec M, Streb J, Halon A, Jach R (2023) Triage strategies for Non-16/Non-18 HPV-Positive women in primary HPV-Based cervical Cancer screening: p16/Ki67 dual stain vs. Cytol Cancers (Basel) 15(20):5095. https://doi.org/10.3390/cancers15205095. PMID: 37894462; PMCID: PMC10605570CrossRef Mazurec K, Trzeszcz M, Mazurec M, Streb J, Halon A, Jach R (2023) Triage strategies for Non-16/Non-18 HPV-Positive women in primary HPV-Based cervical Cancer screening: p16/Ki67 dual stain vs. Cytol Cancers (Basel) 15(20):5095. https://​doi.​org/​10.​3390/​cancers15205095. PMID: 37894462; PMCID: PMC10605570CrossRef
29.
go back to reference Lau G, Abou-Alfa GK, Cheng AL, Sukeepaisarnjaroen W, Dao TV, Kang YK, Thungappa SC, Kudo M, Sangro B, Kelley RK, Furuse J, Park JW, Sunpaweravong P, Fasolo A, Yau T, Kawaoka T, Azevedo S, Reig M, Assenat E, Yarchoan M, He AR, Makowsky M, Gupta C, Negro A, Chan SL Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. J Hepatol 2024 Jul 30:S0168-8278(24)02424-3. https://doi.org/10.1016/j.jhep.2024.07.017. Epub ahead of print. PMID: 39089633. Lau G, Abou-Alfa GK, Cheng AL, Sukeepaisarnjaroen W, Dao TV, Kang YK, Thungappa SC, Kudo M, Sangro B, Kelley RK, Furuse J, Park JW, Sunpaweravong P, Fasolo A, Yau T, Kawaoka T, Azevedo S, Reig M, Assenat E, Yarchoan M, He AR, Makowsky M, Gupta C, Negro A, Chan SL Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. J Hepatol 2024 Jul 30:S0168-8278(24)02424-3. https://​doi.​org/​10.​1016/​j.​jhep.​2024.​07.​017. Epub ahead of print. PMID: 39089633.
30.
go back to reference Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, Yanez Ruiz E, Maruzzo M, Suarez Zaizar A, Fein LE, Schutz FA, Heng DYC, Wang F, Mataveli F, Chang YL, van Kooten Losio M, Suarez C, Motzer RJ (2023) COSMIC-313 investigators. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med 388(19):1767–1778. https://doi.org/10.1056/NEJMoa2212851. PMID: 37163623; PMCID: PMC10257898CrossRefPubMedPubMedCentral Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, Yanez Ruiz E, Maruzzo M, Suarez Zaizar A, Fein LE, Schutz FA, Heng DYC, Wang F, Mataveli F, Chang YL, van Kooten Losio M, Suarez C, Motzer RJ (2023) COSMIC-313 investigators. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med 388(19):1767–1778. https://​doi.​org/​10.​1056/​NEJMoa2212851. PMID: 37163623; PMCID: PMC10257898CrossRefPubMedPubMedCentral
32.
go back to reference Di Nunno V, Mollica V, Schiavina R, Nobili E, Fiorentino M, Brunocilla E, Ardizzoni A, Massari F (2020) Improving IMDC Prognostic Prediction through evaluation of initial site of metastasis in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer 18(2):e83–e90 Epub 2019 Aug 20. PMID: 31753738CrossRefPubMed Di Nunno V, Mollica V, Schiavina R, Nobili E, Fiorentino M, Brunocilla E, Ardizzoni A, Massari F (2020) Improving IMDC Prognostic Prediction through evaluation of initial site of metastasis in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer 18(2):e83–e90 Epub 2019 Aug 20. PMID: 31753738CrossRefPubMed
Metadata
Title
Metastatic sites and clinical outcomes in renal cell carcinoma patients receiving immune-based combinations: the MOUSEION-08 study
Authors
Alessandro Rizzo
Fernando Sabino Marques Monteiro
Veronica Mollica
Oronzo Brunetti
Elsa Vitale
Angela Monica Sciacovelli
Andrey Soares
Francesco Massari
Matteo Santoni
Publication date
01-02-2025
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 1/2025
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-024-10327-w

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