OBJECTIVES : The IMDC risk model, a well-established prognostic model for mRCC, provides benchmarks for trial design, patient counseling, and risk-specific treatments. Based on six risk factors, the IMDC model categorizes patients as favorable (no factors), intermediate (1 or 2 factors), or poor (≥3 factors). To date, limited studies have examined heterogeneity in the IR group. This study assessed patient characteristics and clinical heterogeneity among mRCC patients in the IMDC IR group who received first-line sunitinib therapy in the real-world setting.

METHODS : Clear cell mRCC patients classified as IR who initiated sunitinib as first-line therapy in 2010-2018 were included in this retrospective analysis. Median overall survival (OS) and median time to treatment discontinuation (TTD) from sunitinib initiation was estimated using Kaplan-Meier analysis.

RESULTS : Among patients classified as IR (n=885), the most common risk factors were <1 year from diagnosis to treatment (65%) and anemia (50%). There were 458 and 427 pts in the IMDC IR group who had 1 vs 2 risk factors, respectively. Patients with 1 vs 2 risk factors had significantly lower proportion of brain metastases (8.3% vs 13.5%, P=0.03) and bone metastases (32.3% vs 41.9%, P<0.01), and higher proportion of prior nephrectomy (91.7% vs 81.5%, P<0.01) and prior IL-2/IFN therapy (5.7% vs 2.1%, P<0.01). For patients with 1 vs 2 risk factors, the median OS (95% CI) was 35.1 (31.7-39.6) vs 21.9 (18.5-25.8) months (P<0.01), and the median TTD (95% CI) was 10.3 (8.7-12.0) vs 6.6 (5.6-7.9) months (P<0.01).

CONCLUSIONS : This real-world study shows that mRCC patients in the IR group are heterogeneous in characteristics and clinical outcomes, with longer OS and TTD in patients with 1 vs 2 risk factors. These findings are consistent with previous analysis of clinical trial data, and should be considered when counseling IMDC IR patients.