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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) - Beyond the Abstract

The IMDC score is the most used prognostic classification for metastatic renal cell carcinoma (mRCC) patients. Still, it was developed in 2009, when vascular endothelial growth factor (VEGF) inhibitors dominated mRCC treatment.1 Its use was then carried over into clinical trials with new-generation TKIs and immune checkpoint inhibitor (ICI)-based combinations.2 The addition of two more prognostic factors such as neutrophil to lymphocyte ratio (NLR) ≥3.2 and the presence of bone metastases provided by the Meet-URO score resulted in higher prognostic accuracy in mRCC patients receiving ≥2nd line nivolumab or cabozantinib in two retrospective analyses and 1st line nivolumab-ipilimumab in an expanded access program.3,4

The Meet-URO score stratifies patients into five prognostic classes and is an easy-to-use prognostic tool.5 Due to the increase in the geriatric population in Western countries and the direct correlation between the occurrence of RCC and older age, RCC is increasingly common in older patients in the real world. Nevertheless, older patients are often underrepresented in clinical trials6,7 and the identification of prognostic factors in older patients with mRCC is still lacking. Only a few studies focused on prognostic factors and models in this setting and suggested the prognostic value of a higher NLR.8


Cabozantinib is currently offered as first-line therapy (in combination with ICIs or as monotherapy) or in later lines as monotherapy, also in elderly patients.9-14

In this study, we aimed to assess the prognostic accuracy of the Meet-URO score in older patients (aged ≥ 70 years) treated with cabozantinib at any therapy line and enrolled in the Italian multicenter observational prospective ZEBRA/Meet-URO-9 study (NCT04416646). The primary endpoint was overall survival (OS) and the discriminative ability by Harrell’s c-index and calibration were assessed to compare the Meet-URO and IMDC scores.

We identified 104 mRCC patients who received cabozantinib as 1st (38%), 2nd (20%), or ≥3rd (41%) line. Most patients were male (73.1%), with a clear-cell histological subtype (87%), and had a previous nephrectomy (82.7%). The median age was 75.8 years (range 70.2-87.4 years). According to the IMDC score, 15.4% of patients were favorable- (all ≥ 2nd line), 65.4% intermediate- and 19.2% poor-risk. Baseline NLR was ≥ 3.2 in 51.9% of patients and bone metastases were present in 40%. According to the Meet-URO score, 10% of patients belonged to group 1, 26% to group 2, 34% to group 3, 26% to group 4, and 8% to group 5.

With a median follow-up of 11.2 months, the median OS (mOS) was 18.4 months. According to the IMDC score, favorable, intermediate, and poor-risk patients had a mOS not reached, of 15.6 and 5.7 months respectively (p = 0.011). According to the Meet-URO score groups, mOS was not reached in both group 1 and group 2, while in group 3, group 4, and group 5 it was 13.6, 12.5, and 3.7 months, respectively (p < 0.001) (Figure 1). The discriminative ability of the Meet-URO score was maintained by merging groups 1-2 vs 3-4 vs 5 (p < 0.001). The c-index for the 5-class and 3-class Meet-URO scores were 0.686 and 0.676 respectively, and 0.622 for the IMDC score.

The prognostic accuracy of the Meet-URO score was also confirmed with the PFS in either its 5-group or 3-group classification compared to the IMDC score (c-index of 0.686 and 0.676 vs 0.622).


Figure 1. Overall survival according to IMDC (A) and Meet-URO scores as 5-groups (B) and 3-groups (C) classification.

In conclusion, our analysis confirmed the prognostic accuracy of the Meet-URO score in older mRCC patients treated with cabozantinib. Moreover, this study's findings represent further evidence in favor of adopting the Meet-URO score in clinical practice to inform patient and clinician decisions given the consistent prognostic stratification and accuracy that has been accumulating in different treatment settings for mRCC.

Written by: Alessandra Damassi,1 Malvina Cremante,1 Alessio Signori,2 Sara Elena Rebuzzi,3 Giuseppe Fornarini,1 Giulia Claire Giudice,4 Marco Maruzzo,5 Giuseppe Procopio,6 Mariella Sorarù,7 Marilena Di Napoli,8 Lucia Fratino,9 Daniele Santini,10 Francesco Grillone,11 Melissa Ballestrin,5 Michele Dionese,5 Cecilia Nasso,12 Fabio Catalano,1 Veronica Murianni,1 Pasquale Rescigno,13 Shobana Anpalakhan,14 Giuseppe Luigi Banna,15 Umberto Basso,5 Sebastiano Buti16

  1. Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
  2. Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy.
  3. Medical Oncology Unit, Ospedale San Paolo, Savona, Italy; Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, Genova, Italy.
  4. Department of Medicine and Surgery, University of Parma, Parma, Italy.
  5. Medical Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.
  6. SS Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
  7. U.O. Oncologia, Ospedale di Camposampiero, Camposampiero, Italy.
  8. Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
  9. Department of Medical Oncology, Centro di Riferimento, Oncologico di Aviano CRO-IRCCS, Aviano, Italy.
  10. UOC Oncologia Medica, "Sapienza University", Polo Pontino, Rome, Italy.
  11. Azienda Ospedaliero-Universitario "Mater Domini", Policlinico of Catanzaro, Catanzaro, Italy.
  12. Medical Oncology Unit, Ospedale Santa Corona, Pietra Ligure, Italy.
  13. Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK; Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.
  14. Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, PO6 3LY, UK.
  15. Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, PO6 3LY, UK; Faculty of Science and Health, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2UP, UK.
  16. Department of Medicine and Surgery, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
References:

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  2. Rizzo A, Mollica V, Santoni M, Rosellini M, Marchetti A, Ricci AD, Grilli G, Greco A, Montironi R, Ardizzoni A, Massari F. Comparative effectiveness of first-line immune checkpoint inhibitors plus tyrosine kinase inhibitors according to IMDC risk groups in metastatic renal cell carcinoma: a meta-analysis. Immunotherapy. 2021;13(9):783-793
  3. 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.
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