Skip to main content
Erschienen in: Targeted Oncology 4/2023

27.06.2023 | Original Research Article

Global Real-World Outcomes of Patients Receiving Immuno-Oncology Combinations for Advanced Renal Cell Carcinoma: The ARON-1 Study

verfasst von: Matteo Santoni, Francesco Massari, Zin W. Myint, Roberto Iacovelli, Martin Pichler, Umberto Basso, Jindrich Kopecky, Jakub Kucharz, Sebastiano Buti, Mimma Rizzo, Luca Galli, Thomas Büttner, Ugo De Giorgi, Ravindran Kanesvaran, Ondřej Fiala, Enrique Grande, Paolo Andrea Zucali, Giuseppe Fornarini, Maria T. Bourlon, Sarah Scagliarini, Javier Molina-Cerrillo, Gaetano Aurilio, Marc R. Matrana, Renate Pichler, Carlo Cattrini, Tomas Büchler, Emmanuel Seront, Fabio Calabrò, Alvaro Pinto, Rossana Berardi, Anca Zgura, Giulia Mammone, Jawaher Ansari, Francesco Atzori, Rita Chiari, Aristotelis Bamias, Orazio Caffo, Giuseppe Procopio, Maria Bassanelli, Sara Merler, Carlo Messina, Zsófia Küronya, Alessandra Mosca, Dipen Bhuva, Nuno Vau, Lorena Incorvaia, Sara Elena Rebuzzi, Giandomenico Roviello, Ignacio Ortego Zabalza, Alessandro Rizzo, Veronica Mollica, Giulia Sorgentoni, Fernando Sabino M. Monteiro, Rodolfo Montironi, Nicola Battelli, Camillo Porta

Erschienen in: Targeted Oncology | Ausgabe 4/2023

Einloggen, um Zugang zu erhalten

Abstract

Background

Immuno-oncology combinations have achieved survival benefits in patients with metastatic renal cell carcinoma (mRCC).

Objective

The ARON-1 study (NCT05287464) was designed to globally collect real-world data on the use of immuno-combinations as first-line therapy for mRCC patients.

Patients and Methods

Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of mRCC treated with first-line immuno-combination therapies were retrospectively included from 47 International Institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB).

Results

A total of 729 patients were included; tumor histology was clear-cell RCC in 86% of cases; 313 patients received dual immuno-oncology (IO + IO) therapy while 416 were treated with IO-tyrosine kinase inhibitor (IO + TKI) combinations. In the overall study population, the median OS and PFS were 36.5 and 15.0 months, respectively. The median OS was longer with IO+TKI compared with IO+IO therapy in the 616 patients with intermediate/poor International mRCC Database Consortium (IMDC) risk criteria (55.7 vs 29.7 months; p = 0.045). OCB was 84% for IO+TKI and 72% for IO + IO combination (p < 0.001).

Conclusions

Our study may suggest that immuno-oncology combinations are effective as first-line therapy in the mRCC real-world context, showing outcome differences between IO + IO and IO + TKI combinations in mRCC subpopulations.

Clinical Trial Registration

NCT05287464.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Santoni M, Piva F, Porta C, Bracarda S, Heng DY, Matrana MR, et al. Artificial neural networks as a way to predict future kidney cancer incidence in the United States. Clin Genitourin Cancer. 2021;19(2):e84–91.CrossRefPubMed Santoni M, Piva F, Porta C, Bracarda S, Heng DY, Matrana MR, et al. Artificial neural networks as a way to predict future kidney cancer incidence in the United States. Clin Genitourin Cancer. 2021;19(2):e84–91.CrossRefPubMed
3.
Zurück zum Zitat Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–75.CrossRefPubMedPubMedCentral Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–75.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.CrossRefPubMed Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.CrossRefPubMed
5.
Zurück zum Zitat Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J ClinOncol. 2010;28(6):1061–8.CrossRef Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J ClinOncol. 2010;28(6):1061–8.CrossRef
6.
Zurück zum Zitat Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRefPubMedPubMedCentral Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103–15.CrossRefPubMedPubMedCentral Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103–15.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393(10189):2404–15.CrossRefPubMed Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393(10189):2404–15.CrossRefPubMed
9.
Zurück zum Zitat Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–27.CrossRefPubMed Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–27.CrossRefPubMed
10.
Zurück zum Zitat Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289–300.CrossRefPubMed Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289–300.CrossRefPubMed
11.
Zurück zum Zitat Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829–41.CrossRefPubMedPubMedCentral Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829–41.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Rizzo A, Mollica V, Dall’Olio FG, Ricci AD, Maggio I, Marchetti A, et al. Quality of life assessment in renal cell carcinoma Phase II and III clinical trials published between 2010 and 2020: a systematic review. Future Oncol. 2021;17(20):2671–81.CrossRefPubMed Rizzo A, Mollica V, Dall’Olio FG, Ricci AD, Maggio I, Marchetti A, et al. Quality of life assessment in renal cell carcinoma Phase II and III clinical trials published between 2010 and 2020: a systematic review. Future Oncol. 2021;17(20):2671–81.CrossRefPubMed
13.
Zurück zum Zitat Rathi N, Maughan BL, Agarwal N, Swami U. The tango of immunotherapy and targeted therapy in metastatic renal cell carcinoma. Transl Cancer Res. 2019;8(8):E1–6.CrossRefPubMedPubMedCentral Rathi N, Maughan BL, Agarwal N, Swami U. The tango of immunotherapy and targeted therapy in metastatic renal cell carcinoma. Transl Cancer Res. 2019;8(8):E1–6.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Heng DY, Mackenzie MJ, Vaishampayan UN, Bjarnason GA, Knox JJ, Tan MH, et al. Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy. Ann Oncol. 2012;23(6):1549–55.CrossRefPubMed Heng DY, Mackenzie MJ, Vaishampayan UN, Bjarnason GA, Knox JJ, Tan MH, et al. Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy. Ann Oncol. 2012;23(6):1549–55.CrossRefPubMed
15.
Zurück zum Zitat Santoni M, Massari F, Bracarda S, Grande E, Matrana MR, Rizzo M, et al. Cabozantinib in patients with advanced renal cell carcinoma primary refractory to first-line immunocombinations or tyrosine kinase inhibitors. Eur Urol Focus. 2022;S2405–4569(22):00049–59. Santoni M, Massari F, Bracarda S, Grande E, Matrana MR, Rizzo M, et al. Cabozantinib in patients with advanced renal cell carcinoma primary refractory to first-line immunocombinations or tyrosine kinase inhibitors. Eur Urol Focus. 2022;S2405–4569(22):00049–59.
16.
Zurück zum Zitat Teishima J, Murata D, Inoue S, Hayashi T, Mita K, Hasegawa Y, et al. Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor. Curr Urol. 2021;15(4):187–92.CrossRefPubMedPubMedCentral Teishima J, Murata D, Inoue S, Hayashi T, Mita K, Hasegawa Y, et al. Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor. Curr Urol. 2021;15(4):187–92.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Gan CL, Dudani S, Wells JC, Donskov F, Pal SK, Dizman N, et al. Cabozantinib real-world effectiveness in the first-through fourth-line settings for the treatment of metastatic renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Cancer Med. 2021;10(4):1212–21.CrossRefPubMedPubMedCentral Gan CL, Dudani S, Wells JC, Donskov F, Pal SK, Dizman N, et al. Cabozantinib real-world effectiveness in the first-through fourth-line settings for the treatment of metastatic renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Cancer Med. 2021;10(4):1212–21.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Ravi P, Mantia C, Su C, Sorenson K, Elhag D, Rathi N, Bakouny Z, Agarwal N, Zakharia Y, Costello BA, McKay RR, Narayan V, Alva A, McGregor BA, Gao X, McDermott DF, Choueiri TK. Evaluation of the safety and efficacy of immunotherapy rechallenge in patients with renal cell carcinoma. JAMA Oncol. 2020;6(10):1606–10.CrossRefPubMedPubMedCentral Ravi P, Mantia C, Su C, Sorenson K, Elhag D, Rathi N, Bakouny Z, Agarwal N, Zakharia Y, Costello BA, McKay RR, Narayan V, Alva A, McGregor BA, Gao X, McDermott DF, Choueiri TK. Evaluation of the safety and efficacy of immunotherapy rechallenge in patients with renal cell carcinoma. JAMA Oncol. 2020;6(10):1606–10.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Santoni M, Massari F, Myint ZW, Iacovelli R, Pichler M, Basso U, et al. Clinico-pathological features influencing the prognostic role of body mass index in patients with advanced renal cell carcinoma treated by immuno-oncology combinations (ARON-1). Clin Genitourin Cancer. 2023;S1558–7673(23):00065–74. Santoni M, Massari F, Myint ZW, Iacovelli R, Pichler M, Basso U, et al. Clinico-pathological features influencing the prognostic role of body mass index in patients with advanced renal cell carcinoma treated by immuno-oncology combinations (ARON-1). Clin Genitourin Cancer. 2023;S1558–7673(23):00065–74.
20.
Zurück zum Zitat Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7.CrossRefPubMedPubMedCentral Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Nemoto Y, Ishihara H, Nakamura K, Tachibana H, Fukuda H, Yoshida K, et al. Efficacy and safety of immunotherapy-based combinations as first-line therapy for metastatic renal cell carcinoma in patients who do not meet trial eligibility criteria. Target Oncol. 2022;17(4):475–82.CrossRefPubMed Nemoto Y, Ishihara H, Nakamura K, Tachibana H, Fukuda H, Yoshida K, et al. Efficacy and safety of immunotherapy-based combinations as first-line therapy for metastatic renal cell carcinoma in patients who do not meet trial eligibility criteria. Target Oncol. 2022;17(4):475–82.CrossRefPubMed
22.
Zurück zum Zitat Ishihara H, Nemoto Y, Nakamura K, Tachibana H, Ikeda T, Fukuda H, et al. Comparison of outcomes between therapeutic combinations based on immune checkpoint inhibitors or tyrosine kinase inhibitor monotherapy for first-line therapy of patients with advanced renal cell carcinoma outside of clinical trials: a real-world retrospective multi-institutional study. Target Oncol. 2023;18(2):209–20.CrossRefPubMed Ishihara H, Nemoto Y, Nakamura K, Tachibana H, Ikeda T, Fukuda H, et al. Comparison of outcomes between therapeutic combinations based on immune checkpoint inhibitors or tyrosine kinase inhibitor monotherapy for first-line therapy of patients with advanced renal cell carcinoma outside of clinical trials: a real-world retrospective multi-institutional study. Target Oncol. 2023;18(2):209–20.CrossRefPubMed
24.
Zurück zum Zitat Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004;171:1071–6.CrossRefPubMed Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004;171:1071–6.CrossRefPubMed
25.
Zurück zum Zitat Heng DY, Wells JC, Rini BI, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur Urol. 2014;66:704–10.CrossRefPubMed Heng DY, Wells JC, Rini BI, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur Urol. 2014;66:704–10.CrossRefPubMed
26.
Zurück zum Zitat Massari F, Di Nunno V, Gatto L, et al. Should CARMENA really change our attitude towards cytoreductive nephrectomy in metastatic renal cell carcinoma? A systematic review and meta-analysis evaluating cytoreductive nephrectomy in the era of targeted therapy. Target Oncol. 2018;13:705–14.CrossRefPubMed Massari F, Di Nunno V, Gatto L, et al. Should CARMENA really change our attitude towards cytoreductive nephrectomy in metastatic renal cell carcinoma? A systematic review and meta-analysis evaluating cytoreductive nephrectomy in the era of targeted therapy. Target Oncol. 2018;13:705–14.CrossRefPubMed
27.
Zurück zum Zitat Motzer RJ, Russo P. Cytoreductive nephrectomy—patient selection is key. N Engl J Med. 2018;379:481–2.CrossRefPubMed Motzer RJ, Russo P. Cytoreductive nephrectomy—patient selection is key. N Engl J Med. 2018;379:481–2.CrossRefPubMed
28.
Zurück zum Zitat Massari F, Rizzo A, Mollica V, Rosellini M, Marchetti A, Ardizzoni A, Santoni M. Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials. Eur J Cancer. 2021;154:120–7.CrossRefPubMed Massari F, Rizzo A, Mollica V, Rosellini M, Marchetti A, Ardizzoni A, Santoni M. Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials. Eur J Cancer. 2021;154:120–7.CrossRefPubMed
29.
Zurück zum Zitat Dudani S, Graham J, Wells JC, Bakouny Z, Pal SK, Dizman N, et al. First-line immuno-oncology combination therapies in metastatic renal-cell carcinoma: results from the international metastatic renal-cell carcinoma database consortium. Eur Urol. 2019;76(6):861–7.CrossRefPubMedPubMedCentral Dudani S, Graham J, Wells JC, Bakouny Z, Pal SK, Dizman N, et al. First-line immuno-oncology combination therapies in metastatic renal-cell carcinoma: results from the international metastatic renal-cell carcinoma database consortium. Eur Urol. 2019;76(6):861–7.CrossRefPubMedPubMedCentral
Metadaten
Titel
Global Real-World Outcomes of Patients Receiving Immuno-Oncology Combinations for Advanced Renal Cell Carcinoma: The ARON-1 Study
verfasst von
Matteo Santoni
Francesco Massari
Zin W. Myint
Roberto Iacovelli
Martin Pichler
Umberto Basso
Jindrich Kopecky
Jakub Kucharz
Sebastiano Buti
Mimma Rizzo
Luca Galli
Thomas Büttner
Ugo De Giorgi
Ravindran Kanesvaran
Ondřej Fiala
Enrique Grande
Paolo Andrea Zucali
Giuseppe Fornarini
Maria T. Bourlon
Sarah Scagliarini
Javier Molina-Cerrillo
Gaetano Aurilio
Marc R. Matrana
Renate Pichler
Carlo Cattrini
Tomas Büchler
Emmanuel Seront
Fabio Calabrò
Alvaro Pinto
Rossana Berardi
Anca Zgura
Giulia Mammone
Jawaher Ansari
Francesco Atzori
Rita Chiari
Aristotelis Bamias
Orazio Caffo
Giuseppe Procopio
Maria Bassanelli
Sara Merler
Carlo Messina
Zsófia Küronya
Alessandra Mosca
Dipen Bhuva
Nuno Vau
Lorena Incorvaia
Sara Elena Rebuzzi
Giandomenico Roviello
Ignacio Ortego Zabalza
Alessandro Rizzo
Veronica Mollica
Giulia Sorgentoni
Fernando Sabino M. Monteiro
Rodolfo Montironi
Nicola Battelli
Camillo Porta
Publikationsdatum
27.06.2023
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 4/2023
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-023-00978-2

Weitere Artikel der Ausgabe 4/2023

Targeted Oncology 4/2023 Zur Ausgabe

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Perioperative Checkpointhemmer-Therapie verbessert NSCLC-Prognose

28.05.2024 NSCLC Nachrichten

Eine perioperative Therapie mit Nivolumab reduziert das Risiko für Rezidive und Todesfälle bei operablem NSCLC im Vergleich zu einer alleinigen neoadjuvanten Chemotherapie um über 40%. Darauf deuten die Resultate der Phase-3-Studie CheckMate 77T.

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

27.05.2024 Blut im Stuhl Nachrichten

Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.