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International Multicenter Real-World REGistry for Patients with Metastatic renAL Cell Carcinoma - Meet-URO 33 Study (REGAL Study) - Beyond the Abstract

Over the last years, immune-checkpoint inhibitors (ICIs) have significantly improved the therapeutic scenario of metastatic renal cell carcinoma (mRCC).1 ICI-based combinations are currently the standard first-line therapy in mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, but tyrosine kinase inhibitors (TKI) monotherapy is still a therapeutic option in selected patients.2

Nowadays, therefore, different therapeutic options are available for the first-line treatment of mRCC patients but head-to-head comparisons between the therapeutic strategies are still lacking.3 Moreover, the identification of prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need.4 In this context, low evidence on prognostic/predictive factors is available, especially for mRCC patients treated with immunotherapy.4

For this reason, a novel prognostic score (Meet-URO score) was developed from a multicentric retrospective Italian study on 571 mRCC patients receiving 2nd line nivolumab.5 The Meet-URO score combines the IMDC score with two well-known prognostic factors, such as the presence of bone metastases and the neutrophil-to-lymphocyte ratio (NLR).

The Meet-URO score demonstrated a higher prognostic accuracy compared with the IMDC score alone, identifying 5 risk groups with distinct survival outcomes.5 The higher prognostic performance of the Meet-URO score compared with the IMDC score has been shown also in mRCC patients treated with 1st line and >2nd line cabozantinib, 1st line nivolumab + ipilumumab, >2nd immuno-combinations and elderly patients.6-9 Therefore, the Meet-URO score has been cited in the European Association of Urology (EAU) RCC guidelines.10

Moreover, few prospective studies on large-scale real-world populations have been conducted to assess the different therapeutic strategies of the current first-line setting. In this context, the ongoing Meet-URO 33 study (REGAL study) is a multicentric prospective/retrospective observational study enrolling mRCC patients treated with 1st line systemic therapy from the 1st of January 2021 according to clinical practice in a real-world setting (Trial Registration: CESC IOV 2023-78).11 Eighty-four Italian centers are included in the study and a study amendment will be submitted to include about 10 European centers.

The primary objective is to identify prognostic and/or potentially predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the Meet-URO score compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile.11

The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients to answer as many clinical questions as possible helping clinicians in the decision-making in clinical practice. Given the observational and prospective nature of the study, further analyses will be conducted, both on the entire cohort and particular subgroups, following the principles of emulating a clinical trial, and developing appropriate ad hoc protocols for each planned comparison.

Main ad-hoc sub-analysis will include the assessment of the prognostic value and the performance of the different therapeutic strategies according to specific clinical factors (e.g. laboratory parameters, nephrectomy, metastatic sites), patients’ categories (e.g. poor-risk category, elderly, non-clear cell histology) and treatment characteristics (e.g. treatment beyond progression, subsequent lines, concomitant therapies, toxicity profile).

The Meet-URO 33 project will also help to improve the Italian network on the mRCC therapeutic management and clinical research, providing also a worldwide contribution for collaborations with other International groups in this setting.

Acknowledgments
The authors thank the Meet-URO (Italian Network For Research In Urologic-Oncology) and all physicians, study teams, and patients participating in this study.

Written by:

  • Sara Elena Rebuzzi, MD, PhD, Medical Oncology Unit, Ospedale San Paolo, Savona, Italy
  • Davide Bimbatti, MD, PhD, IOV - IRCCS, Oncologia 1, Istituto Oncologico Veneto, Padova, Italy
  • Giuseppe Fornarini, MD, Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Umberto Basso, MD, IOV - IRCCS, Oncologia 1, Istituto Oncologico Veneto, Padova, Italy
  • Sebastiano Buti, MD, PhD, Medical Oncology Unit, University Hospital of Parma, Department of Medicine and Surgery, University of Parma, Parma, Italy
  • Alessio Signori, PhD, Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy.
References:

  1. Lombardi P, Filetti M, Falcone R, et al. New first-line immunotherapy-based combinations for metastatic renal cell carcinoma: A systematic review and network meta-analysis. Cancer Treat Rev. 2022;106:102377.
  2. Pan E, Urman D, Malvar C, McKay RR. Managing First-Line Metastatic Renal Cell Carcinoma: Favorable-Risk Disease. Hematol Oncol Clin North Am. 2023;S0889-8588(23)00051-5.
  3. Rebuzzi SE, Fornarini G, Signori A, Rescigno P, Banna GL, Buti S. Banana-shaped survival curves of metastatic renal cell carcinoma treated with first-line immune-combinations, not just a matter of "palateau". Hum Vaccin Immunother. 2024;20(1):2351669. doi:10.1080/21645515.2024.2351669
  4. Dani KA, Rich JM, Kumar SS, Cen H, Duddalwar VA, D'Souza A. Comprehensive Systematic Review of Biomarkers in Metastatic Renal Cell Carcinoma: Predictors, Prognostics, and Therapeutic Monitoring. Cancers (Basel). 2023;15(20):4934. doi:10.3390/cancers15204934
  5. Rebuzzi SE, Signori A, Banna GL, et al. Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study). Ther Adv Med Oncol. 2021;13:17588359211019642.
  6. Rebuzzi SE, Cerbone L, Signori A, et al. Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib. Ther Adv Med Oncol. 2022;14:17588359221079580. doi:10.1177/17588359221079580
  7. Rebuzzi SE, Signori A, Buti S, et al. Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian Expanded Access Program. ESMO Open. 2022;7(6):100634. doi:10.1016/j.esmoop.2022.100634
  8. Damassi A, Cremante M, Signori A, et al. Prognostic Stratification by the Meet-URO Score in Real-World Older Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Cabozantinib: A Subanalysis of the Prospective ZEBRA Study (Meet-URO 9). Clin Genitourin Cancer. 2024;22(2):126-133.e2. doi:10.1016/j.clgc.2023.10.001
  9. He S, Liu H, Chen J, Zeng H. Validation of the Meet-URO score in metastatic clear cell renal cell carcinoma patients receiving second or third-line tyrosine kinase inhibitors-immune checkpoint inhibitors combination therapy. J Transl Med. 2024;22(1):232. doi:10.1186/s12967-024-05014-z
  10. European Association of Urology (EAU) Guidelines on Renal Cell Carcinoma
  11. Rebuzzi SE, Fornarini G, Signori A, et al. International multicenter real-world REGistry for patients with metastatic renAL cell carcinoma - Meet-URO 33 study (REGAL study). BMC Cancer. 2024;24(1):757. doi:10.1186/s12885-024-12319-1.
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