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.
