Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study
IntroductionFour approved immune-based combinations for untreated metastatic renal carcinoma have demonstrated survival benefits. The ARON-1 study (NCT05287464) analyzed real-world data of patients with metastatic renal cell carcinoma receiving first-line immuno-oncology combinations. This sub-analy...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1605282/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839617165691453440 |
|---|---|
| author | Maria T. Bourlon Maria T. Bourlon Luca Galli Enrique Grande Se Hoon Park Bohuslav Melichar Timothy J. Schieber Maria José Juan-Fita Yüksel Ürün Javier Molina-Cerrillo Teresa Alonso-Gordoa Ugo De Giorgi Jakub Kucharz Esther Pérez Calabuig Vincenza Conteduca Tarek Taha Tarek Taha Pasquale Rescigno Hussam Abu-Sini Gian Paolo Spinelli Ray Manneh Kopp Alessia Salfi Dipen Bhuva Paola Valdez-Sandoval Sofia Mendez-Bribiesca Ondrej Fiala Ondrej Fiala Sebastiano Buti Sebastiano Buti Fernando Sabino Marques Monteiro Fernando Sabino Marques Monteiro Aristotelis Bamias Marwan Ghosn Francesco Massari Francesco Massari Jawaher Ansari Matteo Santoni |
| author_facet | Maria T. Bourlon Maria T. Bourlon Luca Galli Enrique Grande Se Hoon Park Bohuslav Melichar Timothy J. Schieber Maria José Juan-Fita Yüksel Ürün Javier Molina-Cerrillo Teresa Alonso-Gordoa Ugo De Giorgi Jakub Kucharz Esther Pérez Calabuig Vincenza Conteduca Tarek Taha Tarek Taha Pasquale Rescigno Hussam Abu-Sini Gian Paolo Spinelli Ray Manneh Kopp Alessia Salfi Dipen Bhuva Paola Valdez-Sandoval Sofia Mendez-Bribiesca Ondrej Fiala Ondrej Fiala Sebastiano Buti Sebastiano Buti Fernando Sabino Marques Monteiro Fernando Sabino Marques Monteiro Aristotelis Bamias Marwan Ghosn Francesco Massari Francesco Massari Jawaher Ansari Matteo Santoni |
| author_sort | Maria T. Bourlon |
| collection | DOAJ |
| description | IntroductionFour approved immune-based combinations for untreated metastatic renal carcinoma have demonstrated survival benefits. The ARON-1 study (NCT05287464) analyzed real-world data of patients with metastatic renal cell carcinoma receiving first-line immuno-oncology combinations. This sub-analysis is focused on the nivolumab plus cabozantinib effectiveness.MethodsWe conducted a retrospective study across 52 centers in 17 countries, including patients with metastatic renal carcinoma treated with first-line nivolumab plus cabozantinib, regardless of histologic characteristics, performance status, or risk by IMDC prognostic model. Patients with incomplete medical data were excluded. The primary objective of this sub-analysis of the ARON-1 study was to evaluate the real-world effectiveness and safety.ResultsA total of 333 patients were treated with nivolumab plus cabozantinib, clinical characteristics included ECOG performance status ≥2 20%, non-clear cell histology 16%, sarcomatoid de-differentiation 12%, and poor-risk by IMDC 28%. At a median follow-up of 15.9 months (95%CI 11.2-44.0), the median overall survival was not reached (40.0–NR), the probability of survival at 2 years was 75%, while median progression free survival was 33.7 months (95%CI 21.1-38.9). In the entire cohort, an objective response was observed in 58%, with 6% complete responses, and a median duration of response of 38.9 months (95%CI 33.7–NR). At multivariate analysis, adverse prognostic factors for overall survival included ECOG performance status ≥2, sarcomatoid de-differentiation, brain and bone metastases, and poor IMDC group. In the safety analysis, the incidence of grade 3 or higher toxicity was 37%, with hypertension and hand-foot syndrome being the most frequent adverse events.ConclusionThe findings in the present real-world study reaffirm the clinical benefits and safety of the nivolumab plus cabozantinib combination across all subgroups, including populations that are generally excluded from clinical trials for whom data is often missing. Poor performance status, sarcomatoid de-differentiation, bone or central nervous system metastases and IMDC poor risk group were confirmed as negative prognostic factors. |
| format | Article |
| id | doaj-art-3f6eda24e00d4dc8a7ac022223bdda0f |
| institution | Matheson Library |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-3f6eda24e00d4dc8a7ac022223bdda0f2025-07-25T04:10:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16052821605282Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 studyMaria T. Bourlon0Maria T. Bourlon1Luca Galli2Enrique Grande3Se Hoon Park4Bohuslav Melichar5Timothy J. Schieber6Maria José Juan-Fita7Yüksel Ürün8Javier Molina-Cerrillo9Teresa Alonso-Gordoa10Ugo De Giorgi11Jakub Kucharz12Esther Pérez Calabuig13Vincenza Conteduca14Tarek Taha15Tarek Taha16Pasquale Rescigno17Hussam Abu-Sini18Gian Paolo Spinelli19Ray Manneh Kopp20Alessia Salfi21Dipen Bhuva22Paola Valdez-Sandoval23Sofia Mendez-Bribiesca24Ondrej Fiala25Ondrej Fiala26Sebastiano Buti27Sebastiano Buti28Fernando Sabino Marques Monteiro29Fernando Sabino Marques Monteiro30Aristotelis Bamias31Marwan Ghosn32Francesco Massari33Francesco Massari34Jawaher Ansari35Matteo Santoni36Department of Hemato-Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, MexicoEscuela de Medicina, Universidad Panamericana, Mexico City, MexicoOncology Unit 2, University Hospital of Pisa, Pisa, ItalyDepartment of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, SpainDepartment of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Oncology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, CzechiaDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, Westwood, KS, United StatesDepartment of Medical Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia, SpainDepartment of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Türkiye0Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain0Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain1Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy2Department of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Warsaw, Poland3Medical Oncology Department, CHU Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain4Unit of Medical Oncology and Biomolecular Therapy and C.R.E.A.T.E - Center for Research and Innovation Medicine, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, Foggia, Italy5The Institute of Cancer Research, London, United Kingdom6Royal Marsden NHS Foundation Trust, London, United Kingdom7Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle upon Tyne, United Kingdom8Oncology Institute, Haifa, Israel9UOC Oncologia Territoriale Ausl Latina, Aprilia, Italy0Clinical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, ColombiaOncology Unit 2, University Hospital of Pisa, Pisa, Italy1Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, IndiaDepartment of Hemato-Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, MexicoDepartment of Hemato-Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico2Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czechia3Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia4Medical Oncology Unit, University Hospital of Parma, Parma, Italy5Department of Medicine and Surgery, University of Parma, Parma, Italy6Genitourinary Cancer Group, Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil7Oncology and Hematology Department, Hospital Sírio Libanês, Brasília, Brazil82nd Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece9Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon0Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy1Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy2Medical Oncology, Tawam Hospital, Al Ain, United Arab Emirates3Medical Oncology Unit, Macerata Hospital, Macerata, ItalyIntroductionFour approved immune-based combinations for untreated metastatic renal carcinoma have demonstrated survival benefits. The ARON-1 study (NCT05287464) analyzed real-world data of patients with metastatic renal cell carcinoma receiving first-line immuno-oncology combinations. This sub-analysis is focused on the nivolumab plus cabozantinib effectiveness.MethodsWe conducted a retrospective study across 52 centers in 17 countries, including patients with metastatic renal carcinoma treated with first-line nivolumab plus cabozantinib, regardless of histologic characteristics, performance status, or risk by IMDC prognostic model. Patients with incomplete medical data were excluded. The primary objective of this sub-analysis of the ARON-1 study was to evaluate the real-world effectiveness and safety.ResultsA total of 333 patients were treated with nivolumab plus cabozantinib, clinical characteristics included ECOG performance status ≥2 20%, non-clear cell histology 16%, sarcomatoid de-differentiation 12%, and poor-risk by IMDC 28%. At a median follow-up of 15.9 months (95%CI 11.2-44.0), the median overall survival was not reached (40.0–NR), the probability of survival at 2 years was 75%, while median progression free survival was 33.7 months (95%CI 21.1-38.9). In the entire cohort, an objective response was observed in 58%, with 6% complete responses, and a median duration of response of 38.9 months (95%CI 33.7–NR). At multivariate analysis, adverse prognostic factors for overall survival included ECOG performance status ≥2, sarcomatoid de-differentiation, brain and bone metastases, and poor IMDC group. In the safety analysis, the incidence of grade 3 or higher toxicity was 37%, with hypertension and hand-foot syndrome being the most frequent adverse events.ConclusionThe findings in the present real-world study reaffirm the clinical benefits and safety of the nivolumab plus cabozantinib combination across all subgroups, including populations that are generally excluded from clinical trials for whom data is often missing. Poor performance status, sarcomatoid de-differentiation, bone or central nervous system metastases and IMDC poor risk group were confirmed as negative prognostic factors.https://www.frontiersin.org/articles/10.3389/fonc.2025.1605282/fullnivolumab plus cabozantinibreal-world evidencemetastatic renal cell carcinomaclear cell renal cell carcinomanon-clear cell renal cell carcinoma |
| spellingShingle | Maria T. Bourlon Maria T. Bourlon Luca Galli Enrique Grande Se Hoon Park Bohuslav Melichar Timothy J. Schieber Maria José Juan-Fita Yüksel Ürün Javier Molina-Cerrillo Teresa Alonso-Gordoa Ugo De Giorgi Jakub Kucharz Esther Pérez Calabuig Vincenza Conteduca Tarek Taha Tarek Taha Pasquale Rescigno Hussam Abu-Sini Gian Paolo Spinelli Ray Manneh Kopp Alessia Salfi Dipen Bhuva Paola Valdez-Sandoval Sofia Mendez-Bribiesca Ondrej Fiala Ondrej Fiala Sebastiano Buti Sebastiano Buti Fernando Sabino Marques Monteiro Fernando Sabino Marques Monteiro Aristotelis Bamias Marwan Ghosn Francesco Massari Francesco Massari Jawaher Ansari Matteo Santoni Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study Frontiers in Oncology nivolumab plus cabozantinib real-world evidence metastatic renal cell carcinoma clear cell renal cell carcinoma non-clear cell renal cell carcinoma |
| title | Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study |
| title_full | Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study |
| title_fullStr | Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study |
| title_full_unstemmed | Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study |
| title_short | Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study |
| title_sort | nivolumab plus cabozantinib in metastatic renal cell carcinoma real world evidence from the international aron 1 study |
| topic | nivolumab plus cabozantinib real-world evidence metastatic renal cell carcinoma clear cell renal cell carcinoma non-clear cell renal cell carcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1605282/full |
| work_keys_str_mv | AT mariatbourlon nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT mariatbourlon nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT lucagalli nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT enriquegrande nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT sehoonpark nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT bohuslavmelichar nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT timothyjschieber nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT mariajosejuanfita nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT yukselurun nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT javiermolinacerrillo nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT teresaalonsogordoa nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT ugodegiorgi nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT jakubkucharz nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT estherperezcalabuig nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT vincenzaconteduca nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT tarektaha nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT tarektaha nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT pasqualerescigno nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT hussamabusini nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT gianpaolospinelli nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT raymannehkopp nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT alessiasalfi nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT dipenbhuva nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT paolavaldezsandoval nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT sofiamendezbribiesca nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT ondrejfiala nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT ondrejfiala nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT sebastianobuti nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT sebastianobuti nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT fernandosabinomarquesmonteiro nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT fernandosabinomarquesmonteiro nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT aristotelisbamias nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT marwanghosn nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT francescomassari nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT francescomassari nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT jawaheransari nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study AT matteosantoni nivolumabpluscabozantinibinmetastaticrenalcellcarcinomarealworldevidencefromtheinternationalaron1study |