Abstract 928: Real-world comparison of first-line treatments for metastatic clear cell renal cell carcinoma (mccRCC)

Abstract Multiple regimens are available for management of mccRCC including either immuno-oncology doublet (IO/IO) or combinations of IO and tyrosine kinase inhibitors (TKI). Clinical trials have compared these regimens to sunitinib, with no direct comparison between them. As such, there is ambiguity among physicians about preferred first-line for mccRCC. We performed a single-institution retrospective study of adults treated in first-line for mccRCC between 1/1/2017 and 1/1/2023. Regimens included IO/IO (ipilimumab/nivolumab I/N) or IO/TKI (pembrolizumab/axitinib P/A, nivolumab/cabozantinib N/C, or pembrolizumab/lenvatinib P/L). We compared efficacy and toxicity endpoints, using Kruskal-Wallis test for medians and Chi-square for categorical variables. 42 patients with median age of 61 (range: 36-95) were included. Patient distribution in IO/IO vs IO/TKI group was 20. 0% vs 30. 8% in International Metastatic Database Consortium (IMDC) favorable risk, 46. 7% vs 38. 5% in intermediate-risk, and 33. 3% vs 30. 8% in poor-risk group. 78. 6% vs 66. 6% of patients had WHO grade 3/4 ccRCC, 18. 8% vs 15. 4% had sarcomatoid features in the IO/IO vs IO/TKI, respectively. 38% (16/42) received I/N, 7% (3/42) N/C, 52% (22/42) P/A, and 2% (1/42) P/L. Median follow-up was 109 weeks. Table-1 compares the efficacy of IO/IO vs IO/TKI. IO-related toxicity, TKI-related toxicity, treatment interruptions, dose reductions, and need for steroids were not significantly different between IO/IO and IO/TKI (p= 0. 240, p=0. 372, p=0. 923, p=1. 00, and p=0. 248, respectively). Genomic characteristics will be reported in poster. Despite small sample size, our real-world data showed that patients treated with IO/IO had significantly worse outcomes compared to those treated with IO/TKI. While this difference may stem from a more aggressive disease in IO/IO group but further insights needs to be obtained through future prospective studies comparing IO/IO and IO/TKI regimens. Variable IO/IO IO/TKI p-value Median treatment duration (weeks) 8. 3 59. 4 0. 001 Disease control rate (complete response + partial response + stable disease) (%) 50. 0 91. 7 0. 024 Time from 1st line to 2nd line therapy (weeks) 14. 6 57. 1 0. 001 Median overall survival (weeks) 63. 6 Not reached 0. 001 Citation Format: Omid Yazdanpanah, Sami Dwabe, Garrett Harada, Steven Seyedin, Nataliya Mar. Real-world comparison of first-line treatments for metastatic clear cell renal cell carcinoma (mccRCC) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 928.