Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation: A Multicenter Retrospective Study

BACKGROUND: Metastatic sarcomatoid renal cell carcinoma (msRCC) is an aggressive disease typically associated with poor outcomes following VEGF-targeted therapies. This study evaluated in real-world outcomes in patients with msRCC based on whether they received treatment with immune checkpoint inhibitors (ICIs). METHODS: We conducted a multi-institutional, retrospective study of patients who received systemic therapy for msRCC between July 2010 and June 2020. In total, 203 patients across 6 US academic centers were included. Patients were categorized into 2 groups based on whether they received ICIs: ICI+ (n=155) and ICI- (n=48). Overall survival (OS) was estimated using the Kaplan-Meier method and measured from the initiation of frontline systemic therapy. Treatment responses were evaluated by investigators at participating centers. RESULTS: After a median follow-up of 48.1 months, OS was significantly longer in the ICI+ group (median OS, 31.0 vs 7.6 months; hazard ratio [HR], 0.38; 95% CI, 0.26-0.56; P<.001). ICI+ status (HR, 0.38; 95% CI, 0.25-0.59; P<.001), non-clear cell or unclassified histology (HR, 2.99; 95% CI, 1.86-4.79; P<.001), and sarcomatoid component ≥25% (HR, 1.69; 95% CI, 1.11-2.59; P=.015) were independently predictive of OS. OS benefit in ICI+ group was maintained in the second line or later (median OS, 39.6 vs 7.6 months; HR, 0.32; 95% CI, 0.21-0.49; P<.001). Among patients with non-clear cell or unclassified histology, the ICI+ group had longer OS (median, 18.1 vs 7.0 months; HR, 0.20; 95% CI, 0.09-0.44; P<.001). Objective (39.4% vs 18.8%; P=.014) and complete (11.0% vs 4.2%; P=.258) response rates were higher in the ICI+ group. CONCLUSIONS: A potential benefit of ICI-based therapy is suggested in both clear cell and non-clear cell msRCC. The benefit was observed in both the first-line setting and in second-line or later lines of therapy.