Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group

Abstract

Background. International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment. Materials and Methods. Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors. Results. Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors. Conclusion. This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes. The Oncologist 2020;25:422-430Implications for Practice: This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4-61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.

Real-World Outcomes in Patients with Metastatic Renal Cell Carcinoma According to Risk Factors: The STAR-TOR Registry

“…Outcomes from this analysis were generally consistent with those from other studies [9][10][11][12][13][14][15], including analyses from other large databases [9,13,14]. A retrospective analysis of the 375 sunitinib-treated patients enrolled in the pivotal sunitinib versus interferon-α Phase III trial reported substantial differences in OS for patients of intermediate risk with 1 RF (IMDC, 28.2 months; MSKCC, 23.1 months) compared with patients with 2 RFs (IMDC, 16.3 months; MSKCC 16.7 months) [11].…”

“…Notably, there was no statistically significant difference in OS for patients with 0 versus 1 RF stratified by IMDC. This suggests that patients with 1 IMDC RF (intermediate-risk group) have similar outcomes to IMDC favorable-risk patients, adding to the evidence that the intermediate group is heterogenous [9][10][11][12][13][14][15]24]. Consistently, OS was significantly longer for patients with 1 IMDC RF than for patients with 2 IMDC RFs.…”

“…A pooled analysis of 6 clinical trials of sunitinib-treated patients reported similar results [12]. Consistently, an analysis of 1769 patients in the IMDC reported significantly longer OS in patients with 1 IMDC RF (35.1 months) compared with patients with 2 IMDC RFs (21.9 months) [13]. A recent, large analysis of 2390 patients enrolled in the RenIS registry and stratified according to MSKCC reported significantly longer OS for patients with 1 RF compared with patients with 2 MSKCC RFs (28.2 vs 16.2 months; p < 0.001) [14].…”

“…Treatment results typically vary according to patient risk groups, with potentially poorer outcomes for patients with ≥4 IMDC RFs or poor risk by MSKCC [8]. Over 50% of patients are classified as intermediate risk according to the IMDC and MSKCC prognostic models [5]; however, an increasing body of evidence suggests that the intermediate-risk group is heterogeneous [9][10][11][12][13][14][15] with important implications for treatment selection, patient counseling and stratification.…”

The Clinical Significance of Routine Risk Categorization in Metastatic Renal Cell Carcinoma and its Impact on Treatment Decision-Making: A Systematic Review

“…It is becoming increasingly apparent that the intermediate risk group (one or two risk factors) is heterogeneous [23,[36][37][38][39]. According to the IMDC and MSKCC models, the majority of patients present with intermediate risk, at 52 and 59% of patients, respectively [34].…”