Avelumab in combination with axitinib and nivolumab in combination with ipilimumab in the first-line treatment of metastatic renal cell carcinoma: a realworld retrospective cohort study

Background: Immunotherapy-based regimens, such as nivolumab plus ipilimumab (Nivo-Ipi) and avelumab plus axitinib (Ave-Axi), are standard first-line treatments for metastatic clear-cell renal cell carcinoma (mRCC) with intermediate or poor IMDC risk. Comparative real-world evidence for these regimens remains limited. Methods: This retrospective cohort study included 102 patients with mRCC treated with Nivo-Ipi (n = 51) or AveAxi (n = 51) from 2018 to 2023. Propensity score matching was used to balance baseline characteristics, including IMDC risk and comorbidities. Primary endpoints were the rate of treatment-related adverse events (TRAEs) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and overall survival (OS). Results: Patient characteristics were balanced across cohorts, with a median age of 63.4 years, 76 % male, and 61 % having chronic cardiovascular diseases. The rate of any grade TRAEs was similar between Nivo-Ipi and Ave-Axi (62.7 % vs. 68.6 %, respectively), as was the rate of grade ≥ 3 TRAEs (11.7 % vs. 17.6 %). Patients treated with Ave-Axi had a significantly extended PFS (15.0 vs 9.7 months; p  0,05). The median OS was not reached. Conclusions: Nivo-Ipi and Ave-Axi are effective and well-tolerated first-line therapies for mRCC in real-world settings. Ave-Axi was associated with a significantly longer PFS and a numerically higher ORR compared to Nivo-Ipi.