Clinico-pathological features influencing the prognostic role of Body Mass Index in patients with advanced Renal Cell Carcinoma treated by immuno-oncology combinations (ARON-1)

Obesity is a well-known risk factor for the development of renal cell carcinoma (RCC), one of the most frequent malignant urogenital tumors. The development of immunotherapy (IO)-based combinations for the treatment of metastatic RCC (mRCC) has led to a marked improvement of patients’ outcomes and quality of life. The ARON- 1 study (NCT05287464) was designed to globally analyze real-world treatment outcomes of mRCC patients receiving first-line immune-based combinations. In this sub-analysis, we investigated the role of body mass index (BMI) in patients treated by immuno-oncology combinations stratified by clinico-pathological features. According to our results, the prognostic significance and the association of BMI with treatment outcome may vary across clinico-pathological mRCC subgroups. Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investi- gated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno- oncology agents (IO + IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first- line therapy for metastatic renal cell carcinoma (mRCC). Patients and Methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. Results: A total of 675 patients were included; BMI was > 25 kg/m 2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI > 25 kg/m 2 versus those with BMI ≤25 kg/m 2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio > 4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P = .044). In the BMI ≤25 kg/m 2 subgroup, significant differences were found between patients with NLR > 4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO + IO versus IO + TKIs combinations (64% vs. 83%, P = .002). Conclusion: Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.