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Comparative Study
. 2025 Jan 3;74(2):65.
doi: 10.1007/s00262-024-03897-x.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study

Giandomenico Roviello  1 , Javier Molina-Cerrillo  2   3 , Francesco Massari  4   5 , Linda Cerbone  6 , Ondrej Fiala  7   8 , Giuseppe Fornarini  9 , Fernando Sabino Marques Monteiro  10   11 , Carlo Cattrini  12 , Johannes Landmesser  13 , Carlo Messina  14 , Anca Zgura  15 , Sara Elena Rebuzzi  16   17 , Andrey Soares  10   18 , Francesco Carrozza  19 , Jawaher Ansari  20 , Francesco Grillone  21 , Zsófia Küronya  22 , Lorena Incorvaia  23 , Dipen Bhuva  24 , Cinzia Ortega  25 , Cecilia Nasso  26 , Ravindran Kanesvaran  27 , Ilaria Zampiva  28 , Camillo Porta  29 , Sebastiano Buti  30 , Matteo Santoni  31
Affiliations
Comparative Study

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study

Giandomenico Roviello et al. Cancer Immunol Immunother. .

Abstract

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials and methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate. We carried out a survival analysis by a Cox regression model.

Results: A total of 524 favorable-risk patients were included in the analysis. After a median follow-up of 37.2 months, the median OS in the overall population was 56.1 months. There was no significant difference in OS between patients receiving sunitinib and those receiving TKI + ICI combinations (p = 0.761). Patients on TKI + ICI had significantly longer PFS compared to patient treated with sunitinib (30.7 vs 22.9 months, p = 0.007). Analysis of OS and PFS based on metastatic site revealed that patients with bone metastases benefited more from ICI plus TKI (56 patients with bone metastases receiving IO + TKI, 38 received pembrolizumab plus axitinib, 15 cabozantinib plus nivolumab and 3 pembrolizumab plus lenvatinib), while sunitinib was more effective for pancreatic and glandular metastases. Additionally, the number of metastatic sites played a role, with TKI plus ICI showing superiority in patients with a single metastatic site. The time from RCC diagnosis to metastatic disease also impacted outcomes, with TKI plus ICI being more effective in patients with a shorter interval (i.e., < 36 months).

Conclusions: The choice between upfront combination or monotherapy for metastatic favorable prognosis RCC remains a current issue. While combination therapy offers prolonged PFS, it does not necessarily translate to improve OS compared to sunitinib. This real-world study supports the superiority in terms of PFS of TKI plus ICI vs TKI monotherapy but not in OS. Probable, other clinical factors should be taking into account to make clinical treatment decisions in this setting.

Keywords: ARON-1 study; Good favorable-risk IMDC criteria; Immune-based combinations; Immunotherapy; Renal cell carcinoma.

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Conflict of interest statement

Declarations. Conflicts of Interest: Javier Molina-Cerrillo declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen and BMS. JMC has received research grants from Pfizer, IPSEN and Roche Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work. Linda Cerbone has received honoraria for advisory boards, speaker engagements and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, A.A.A.; past MSD employee in Medical Affairs. Ondrej Fiala received honoraria from Novartis, Janssen, Merck and Pfizer for consultations and lectures unrelated to this project. Fernando Sabino M. Monteiro has received research support from Janssen, Merck Sharp Dome and honoraria from Janssen, Ipsen, Bristol Myers Squibb and Merck Sharp Dome, all unrelated to the present paper. R. Kanesvaran has received fees for speaker bureau and advisory board activities from the following companies; Pfizer, MSD, BMS, Eisai, Ipsen, Johnson and Johnson, Merck, Amgen, Astellas and Bayer. Camillo Porta has received honoraria from Angelini Pharma, AstraZeneca, BMS, Eisai, Ipsen and MSD and acted as a Protocol Steering Committee Member for BMS, Eisai and MSD. Sebastiano Buti has received honoraria for speaking at scientific events and advisory roles from AstraZeneca, Bristol Myers Squibb, Ipsen, Merck, Eisai, MSD, Novartis and Pfizer and research funding from Novartis and Pfizer. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, A.A.A. and Bayer, all unrelated to the present paper. The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Overall survival and progression-free survival in favorable-risk RCC patients treated by IO + TKI or sunitinib
Fig. 2
Fig. 2
Progression-free survival in favorable-risk RCC patients treated by IO + TKI or sunitinib based on metastatic site and number of sites
Fig. 3
Fig. 3
1-year and 2-year OS rates according to the time from RCC diagnosis to metastatic disease in favorable-risk patients treated by IO + TKI or sunitinib
Fig. 4
Fig. 4
Rate of CR and PD as best response by type first-line therapy
See this image and copyright information in PMC

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