Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma

Abstract Introduction Systemic therapy for advanced renal cell carcinoma (aRCC) has become increasingly diverse. In the 1st-line setting, various combination therapies are available, with little comparative data on the efficacy of the therapies. The aim of this study was to compare the current 1st-l...

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Main Authors: Maximilian Haack, Stephanie Neuberger, Jan Hendrik Boerner, Stefanie Ziewers, Gregor Duwe, Robert Dotzauer, Axel Haferkamp, Rene Mager
Format: Article
Language:English
Published: Springer 2025-03-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02131-z
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author Maximilian Haack
Stephanie Neuberger
Jan Hendrik Boerner
Stefanie Ziewers
Gregor Duwe
Robert Dotzauer
Axel Haferkamp
Rene Mager
author_facet Maximilian Haack
Stephanie Neuberger
Jan Hendrik Boerner
Stefanie Ziewers
Gregor Duwe
Robert Dotzauer
Axel Haferkamp
Rene Mager
author_sort Maximilian Haack
collection DOAJ
description Abstract Introduction Systemic therapy for advanced renal cell carcinoma (aRCC) has become increasingly diverse. In the 1st-line setting, various combination therapies are available, with little comparative data on the efficacy of the therapies. The aim of this study was to compare the current 1st-line combination therapies under real-life conditions and to investigate risk factors in the patient population. Methods Patients with aRCC who started 1st-line IO/IO or IO/TKI combination  therapy between 03/2019 and 10/2023 were included. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were time on treatment (ToT), duration of response (DoR), subsequent therapies, the evaluation of risk factors and their influence on PFS and OS. Survival data were analysed using Kaplan–Meier estimates with log-rank tests, risk factors for PFS and OS using Cox regression analysis. Results A total of 59 patients, mainly men (79.7%) with a median age of 64.8 years were included. The median follow-up was 21 months. The comparison of IO/IO vs. IO/TKI demonstrated a median PFS of 6 (2.08–9.92) vs. 14 (9.06–18.94) months (47 events; HR IO/TKI vs. IO/IO: 0.53 (0.29–0.99); p = 0.039) and a median OS of 20 (15.07–24.94) vs. 33 (21.68–44.32) months (32 deaths; HR IO/TKI vs. IO/IO: 0.74 (0.36–1.51); p = 0.403). Off all risk factors analysed only synchronous metastases proved to be of independent predictive value for PFS (HR 2.38; 95% CI 1.11–5.11; p = 0.026) and OS (HR 3.47; 95% CI 1.15–10.44; p = 0.027). Conclusion An IO/TKI therapy showed a significantly improved PFS in the real-world setting compared to an IO/IO combination. In terms of OS, the improved treatment response of the IO/TKI group did not prevail.
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spelling doaj-art-e6449a76f1844e959890e3df7fc5536b2025-08-20T02:41:32ZengSpringerDiscover Oncology2730-60112025-03-0116111210.1007/s12672-025-02131-zReal-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinomaMaximilian Haack0Stephanie Neuberger1Jan Hendrik Boerner2Stefanie Ziewers3Gregor Duwe4Robert Dotzauer5Axel Haferkamp6Rene Mager7Department of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterDepartment of Urology and Pediatric Urology, Johannes Gutenberg University Medical CenterAbstract Introduction Systemic therapy for advanced renal cell carcinoma (aRCC) has become increasingly diverse. In the 1st-line setting, various combination therapies are available, with little comparative data on the efficacy of the therapies. The aim of this study was to compare the current 1st-line combination therapies under real-life conditions and to investigate risk factors in the patient population. Methods Patients with aRCC who started 1st-line IO/IO or IO/TKI combination  therapy between 03/2019 and 10/2023 were included. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were time on treatment (ToT), duration of response (DoR), subsequent therapies, the evaluation of risk factors and their influence on PFS and OS. Survival data were analysed using Kaplan–Meier estimates with log-rank tests, risk factors for PFS and OS using Cox regression analysis. Results A total of 59 patients, mainly men (79.7%) with a median age of 64.8 years were included. The median follow-up was 21 months. The comparison of IO/IO vs. IO/TKI demonstrated a median PFS of 6 (2.08–9.92) vs. 14 (9.06–18.94) months (47 events; HR IO/TKI vs. IO/IO: 0.53 (0.29–0.99); p = 0.039) and a median OS of 20 (15.07–24.94) vs. 33 (21.68–44.32) months (32 deaths; HR IO/TKI vs. IO/IO: 0.74 (0.36–1.51); p = 0.403). Off all risk factors analysed only synchronous metastases proved to be of independent predictive value for PFS (HR 2.38; 95% CI 1.11–5.11; p = 0.026) and OS (HR 3.47; 95% CI 1.15–10.44; p = 0.027). Conclusion An IO/TKI therapy showed a significantly improved PFS in the real-world setting compared to an IO/IO combination. In terms of OS, the improved treatment response of the IO/TKI group did not prevail.https://doi.org/10.1007/s12672-025-02131-zAdvanced renal cell carcinomaImmunotherapyTargeted therapyReal-world data
spellingShingle Maximilian Haack
Stephanie Neuberger
Jan Hendrik Boerner
Stefanie Ziewers
Gregor Duwe
Robert Dotzauer
Axel Haferkamp
Rene Mager
Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma
Discover Oncology
Advanced renal cell carcinoma
Immunotherapy
Targeted therapy
Real-world data
title Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma
title_full Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma
title_fullStr Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma
title_full_unstemmed Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma
title_short Real-world comparison of the efficacy of first-line therapies and the influence of risk factors in advanced renal cell carcinoma
title_sort real world comparison of the efficacy of first line therapies and the influence of risk factors in advanced renal cell carcinoma
topic Advanced renal cell carcinoma
Immunotherapy
Targeted therapy
Real-world data
url https://doi.org/10.1007/s12672-025-02131-z
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