BACKGROUND: The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting. METHODS: Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests. RESULTS: A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS. CONCLUSIONS: In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.

• Klíčová slova
• ARON-1 study, Axitinib plus pembrolizumab, Cabozantinib plus nivolumab, Immune-oncology combinations,
• MeSH
• anilidy * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• axitinib * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• karcinom z renálních buněk * farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   patologie   mortalita   MeSH
• nivolumab * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH
• Názvy látek
• anilidy * MeSH
• axitinib * MeSH
• cabozantinib MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• nivolumab * MeSH
• pembrolizumab MeSH Prohlížeč
• pyridiny MeSH

Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.

• Klíčová slova
• Immune checkpoint inhibitors, Metastasis, Network meta-analysis, Renal cell carcinoma,
• MeSH
• ipilimumab MeSH
• karcinom z renálních buněk * farmakoterapie   MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   MeSH
• následné studie MeSH
• nivolumab MeSH
• patologická kompletní odpověď MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• síťová metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• ipilimumab MeSH
• nivolumab MeSH