Geographical differences in the management of metastatic de novo renal cell carcinoma in the era of immune-combinations
Abstract
Background: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations. This sub-analysis is focused on the role of upfront or delayed partial or radical CN in three geographical areas (Western Europe, Eastern Europe, America/Asia).
Methods: We conducted a multicenter retrospective observational study in mRCC patients treated with first-line immune combinations from 55 centers in 19 countries. From 1152 patients in the ARON-1 dataset, we selected 651 patients with de novo mRCC. 255 patients (39%) had undergone CN, partial in 14% and radical in 86% of cases; 396 patients (61%) received first-line immune-combinations without previous nephrectomy.
Results: Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months and not reached (NR) in the CN subgroup and 24.0 months in the no CN subgroup, respectively (P<0.001). Median OS from the start of first-line therapy was NR in patients who underwent CN and 22.4 months in the no CN subgroup (P<0.001). Patients who underwent CN reported longer OS compared to no CN in all the three geographical areas. Conclusions: No significant differences in terms of patients' outcome seem to clearly emerge, even if the rate CN and the choice of the type of first-line immune-based combination varies across the different Cancer Centers participating in the ARON-1 project.
Systemic Immune-Inflammation Index in Patients Treated With First-Line Immune Combinations for Metastatic Renal Cell Carcinoma: Insights From the ARON-1 Study
**Abstract**
**Background:** Renal cell carcinoma (RCC) is one of the most common urological cancers globally, with increasing incidence. Immunotherapy, either alone or in combination with tyrosine kinase inhibitors (TKIs), has become a key treatment option for advanced RCC, though head-to-head comparisons are lacking. Real-world evidence is essential to guide treatment decisions.
**Objective:** This study aimed to assess outcomes in advanced RCC patients treated with first-line immune-oncology (IO) combinations or IO-TKI combinations.
**Design, Setting, and Participants:** Data were retrospectively collected from 930 advanced RCC patients (654 intermediate-risk, 276 poor-risk) from 58 centers in 20 countries. Variables such as sarcomatoid differentiation, prior nephrectomy, metastatic sites, and biochemical markers were included.
**Outcome Measurements and Statistical Analysis:** Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The median follow-up was 18.7 months.
**Results:** In intermediate-risk patients, IO + TKI therapy was associated with significantly longer OS (55.7 vs 40.2 months; p = 0.047) and PFS (30.7 vs 13.2 months; p < 0.001) compared to IO + IO therapy. In the poor-risk subgroup, no significant differences in OS or PFS were observed between the two treatment approaches. The retrospective nature of the study represents a limitation. **Conclusions:** In real-world data, intermediate-risk RCC patients benefit more from IO + TKI combinations compared to IO + IO combinations, with longer OS and PFS. No significant differences were found in poor-risk patients. These findings may influence treatment decision-making in clinical practice. **Patient Summary:** This study analyzed data from 930 renal cancer patients across 20 countries to compare treatment strategies. Intermediate-risk patients benefited more from the combination of immunotherapy with antiangiogenic therapy (IO + TKI) than from dual immunotherapy (IO + IO). No such differences were observed in poor-risk patients, informing treatment choices for these populations.
Geographical differences in the management of metastatic de novo renal cell carcinoma in the era of immune-combinations
**Abstract**
**Background:** The introduction of immune-based combinations has transformed the upfront treatment of metastatic renal cell carcinoma (mRCC), though the role of cytoreductive nephrectomy (CN) remains debated. This sub-analysis of the ARON-1 study (NCT05287464) evaluates the impact of upfront or delayed partial or radical CN in mRCC patients across three geographical regions (Western Europe, Eastern Europe, and America/Asia).
**Methods:** A multicenter, retrospective observational study was conducted involving mRCC patients treated with first-line immune-combination therapies across 55 centers in 19 countries. From the ARON-1 dataset of 1152 patients, 651 de novo mRCC patients were selected. Among them, 255 (39%) underwent CN (14% partial, 86% radical), while 396 (61%) received first-line immune therapies without prior nephrectomy.
**Results:** Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months in the CN group and 24.0 months in the no CN group (P<0.001). From the start of first-line therapy, OS was not reached (NR) in the CN group and was 22.4 months in the no CN group (P<0.001). CN was associated with improved OS across all geographical regions analyzed. **Conclusions:** While CN rates and the choice of immune-based first-line combinations varied across centers, patients who underwent CN experienced better survival outcomes. These findings suggest a potential benefit of CN in mRCC patients receiving immune-combination therapies.
Real-world Outcome of Patients with Advanced Renal Cell Carcinoma and Intermediate- or Poor-risk International Metastatic Renal Cell Carcinoma Database Consortium Criteria Treated by Immune-oncology Combinations: Differential Effectiveness by Risk Group?
**Abstract**
**Background:** Immuno-oncology (IO) combination therapies have demonstrated survival benefits in patients with metastatic renal cell carcinoma (mRCC).
**Objective:** The ARON-1 study (NCT05287464) aimed to collect real-world data on the effectiveness of first-line IO combination therapies in mRCC patients globally.
**Patients and Methods:** This retrospective analysis included 729 patients aged ≥18 years with cytologically or histologically confirmed mRCC, treated with IO combinations across 47 international institutions in 16 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB).
**Results:** Of the 729 patients, 86% had clear-cell RCC. IO + IO therapy was administered to 313 patients, while 416 received IO + tyrosine kinase inhibitor (IO + TKI) therapy. The median OS and PFS in the overall population were 36.5 and 15.0 months, respectively. Among 616 patients with intermediate/poor International mRCC Database Consortium (IMDC) risk, IO + TKI therapy was associated with a significantly longer median OS compared to IO + IO (55.7 vs 29.7 months; p = 0.045). OCB was 84% with IO + TKI and 72% with IO + IO (p < 0.001). **Conclusions:** The ARON-1 study suggests that IO combinations are effective as first-line therapy for mRCC in a real-world setting, with notable differences in outcomes between IO + IO and IO + TKI therapies in specific patient subgroups.
Global Real-World Outcomes of Patients Receiving Immuno-Oncology Combinations for Advanced Renal Cell Carcinoma: The ARON-1 Study.
Background: Immuno-oncology combination therapies have demonstrated survival benefits in patients with metastatic renal cell carcinoma (mRCC).
Objective: The ARON-1 study (NCT05287464) aimed to collect global real-world data on the use of immuno-combination therapies as first-line treatment for mRCC.
Patients and Methods: This retrospective study included 729 mRCC patients aged ≥ 18 years, with a confirmed diagnosis of mRCC, from 47 institutions across 16 countries. Patients were treated with either dual immuno-oncology (IO + IO) or immuno-oncology and tyrosine kinase inhibitor (IO + TKI) combinations. Outcomes included overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB).
Results: Of the 729 patients, 86% had clear-cell histology. IO + IO therapy was used in 313 patients, and 416 received IO + TKI. The overall median OS was 36.5 months, and median PFS was 15.0 months. Among the 616 patients with intermediate/poor IMDC risk, median OS was significantly longer with IO + TKI compared to IO + IO therapy (55.7 vs. 29.7 months; p = 0.045). OCB was higher for IO + TKI (84%) compared to IO + IO (72%; p < 0.001). Conclusions: Immuno-oncology combinations are effective as first-line therapies in real-world mRCC patients, with IO + TKI showing superior outcomes compared to IO + IO in specific subpopulations.
