Pembrolizumab-axitinib versus nivolumab-cabozantinib as first-line therapy in patients withmetastatic renal cell carcinoma: a retrospective real-world comparison (ARON-1)
Immune-based Combinations in Intermediate-/Poor-risk Patients with Non-clear Cell RenalCell Carcinoma: Results from the ARON-1 Study
Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study
mRNA expression, tumor heterogeneity, and response to therapy inpatients with advanced renal cell carcinoma treated with immune-basedcombinations (ARON-1α)
Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)
Clinical features and response to immune combinations in patients with renal cell carcinoma and sarcomatoid de-differentiation (ARON-1 study).
Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations
Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)
Abstract
Background: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care.
Objective: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy.
Methods: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson’s correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.
Results: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). Conclusions: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.
Papillary Renal Cell Carcinoma: Outcomes for Patients Receiving First-line Immune-based Combinations or Tyrosine Kinase Inhibitors from the ARON-1 Study
Background and objective: Papillary renal cell carcinoma (pRCC) is the most frequent histological subtype of non-clear cell RCC (nccRCC). Owing to the heterogeneity of nccRCC, patients are often excluded from large phase 3 trials focused on clear cell RCC, so treatment options for nccRCC remain limited. Our aim was to investigate the efficacy of first-line treatment with tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO)-based combinations in patients with pRCC.
Methods: We performed a multicenter retrospective analysis of real-world data collected for patients with advanced pRCC treated in 40 centers in 12 countries as part of the ARON-1 project (NCT05287464). The primary endpoints were overall survival (OS), progression-free survival (PFS), the overall response rate (ORR), and time to second progression (PFS2). OS, PFS, and PFS2 were estimated using the Kaplan-Meier method and results were compared between the treatment groups using a log-rank test. Univariate and multivariable analyses were carried out using Cox proportional-hazard models.
Key findings and limitations: We included 200 patients with metastatic pRCC, of whom 73 were treated with IO-based combinations and 127 with TKIs. Median OS was 22.5 mo in the TKI group 28.8 mo in the IO group (p = 0.081). Median PFS was 6.4 mo in the TKI group and 17.4 mo in the IO group (p < 0.001). The ORR was higher in the IO group than in the TKI group (41% vs 27%; p = 0.037). Conclusions and clinical implications: Our results show that IO-based combinations have superior efficacy outcomes to TKIs for first-line treatment of metastatic pRCC. Patient summary: The ARON-1 project collects clinical data for patients with kidney cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic kidney cancer of a specific subtype to evaluate the efficacy of different first-line treatments. Patients treated with immune-based combinations had better outcomes than patients treated with tyrosine kinase inhibitors. Keywords: ARON-1; Immuno-oncology combinations; Immunotherapy; Papillary renal cell carcinoma; Survival; Tyrosine kinase inhibitors.
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:** Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC). The systemic immune-inflammation index (SII), a prognostic marker for various malignancies, has limited and conflicting data regarding its value in mRCC patients treated with immunotherapy.
**Methods:** We retrospectively analyzed data from 1034 mRCC patients across 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to first-line treatment, with a cut-off value of 1265 determined by receiver operating characteristic (ROC) analysis. The primary objective was to assess the outcomes of patients treated with immunotherapy.
**Results:** After a median follow-up of 26.7 months, the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. Patients with low SII had significantly longer OS (55.7 vs. 22.2 months, P < .001), improved PFS (20.8 vs. 8.5 months, P < .001), and a higher overall response rate (52% vs. 37%, P = .033) compared to those with high SII. **Conclusion:** High SII is associated with poorer outcomes in mRCC patients treated with immunotherapy. SII may serve as a simple, accessible prognostic tool in clinical practice. **Keywords:** Immune checkpoint inhibitors; Prognostic biomarker; Systemic immune-inflammation index; Metastatic renal cell carcinoma.
