Outcomes of patients with metastatic renal cell carcinoma with sarcomatoid dedifferentiation to immune checkpoint inhibitors

Introduction: Metastatic renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is associated with poor survival outcomes. We aimed to analyze the efficacy and safety of immune checkpoint inhibitors (ICI) in patients with sRCC comparing clear-cell (sccRCC) to non-clear cell epithelial histology (snccRCC). Methods: We performed retrospective analysis of sRCC patients who received ICI at MD Anderson Cancer Center (n = 48, 41 with ccRCC and 7 with nccRCC) to determine the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, we performed a prespecified multivariable Cox regression comparing survival outcomes between sccRCC and snccRCC. Results: The ORR for the entire cohort was 35.4% (95% confidence interval [CI]: 23.4%, 49.6%), including 8 (16.7%) patients (95% CI: 8.7%, 29.6%) who achieved a complete remission. The disease control rate was 52% (95% CI: 38.3%, 65.5%). In patients with sccRCC, the ORR was 39% (95% CI: 25.7%, 54.3%) and disease control rate 58.5% (43.4%, 72.2%). Among 7 snccRCC patients, only one (14.3%) achieved an objective partial response. At a median follow-up of 51.1 months, the median PFS was 4.9 months (95% CI: 2.7, 16.3) and the median OS was 28.4 months (95% CI: 15.8, NA) for the entire cohort. For patients with sccRCC, the median PFS was 8.9 months, with median OS of 30.1 months, compared with median PFS of 2.3 months (HR 0.25 [95% CI: 0.08, 0.78]; P= 0.0145) and median OS of 6.7 months (HR 0.13 [95% CI 0.04, 0.44]; P=0.0009) for patients with snccRCC. Conclusion: ICIs appear to be effective in sccRCC while the treatment of snccRCC remains challenging.