Abstract

Abstract Background Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. Methods We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. Results Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4 months (95% CI: 1.6–9.1) for the IO-IO group and 5.6 (95% CI: 3.4–12.0) for the IO + TKI group. Median OS was 24.2 months (95% CI: 7.5–NA) for the IO-IO group and 23.4 (95% CI: 18.8–NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). Conclusions There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.