Journal of the National Comprehensive Cancer Network : JNCCN · 2026
Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation: A Multicenter Retrospective Study.
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Gopalakrishnan Dharmesh, Fujiwara Yu, Collier Katharine A, Park Joseph J, Zaemes Jacob P, Lam Elaine T, Alaklabi Sabah, Jaeger Ellen B, Barata Pedro C, Kauffman Eric C, Atkins Michael B, Alva Ajjai, Yang Yuanquan, George Saby
Аннотация
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.
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.