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)

Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated 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.