Characterization of Patients With Poor-Risk Metastatic Renal-Cell Carcinoma: Results From a Pooled Clinical Trials Database

Given limited prospective clinical trial data of poor-risk patients with metastatic renal-cell carcinoma, we sought to provide a comprehensive analysis of this patient population, defined by 3 widely used prognostic models, in the setting of targeted therapy. Our results indicate that the International Metastatic Renal Cell Carcinoma Database Consortium, Memorial Sloan Kettering Cancer Center, and Hudes risk models have comparable discriminative ability. We also show that a subset of poor-risk patients experiences a prolonged clinical benefit and needs to be further explored. Background: Poor-risk patients with metastatic renal-cell carcinoma remain poorly characterized in prospective clinical trials. Therefore, we sought to provide a comprehensive analysis of this patient population, defined by 3 widely used prognostic models, treated with targeted therapy. Patients and Methods: We conducted a pooled retrospective analysis of 4736 metastatic renal-cell carcinoma patients treated on phase 2 and 3 clinical trials. Poor-risk patients were defined according to the Memorial Sloan Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), and Hudes risk models. Baseline characteristics, overall survival, progression-free survival, objective response rate, and adverse events were reported in poor-risk patients defined by each of the 3 models. The concordance (C)-index was used to assess the prognostic performance of the models. A subset of poor-risk patients who continued to receive treatment for > 12 months was characterized. Results: Overall, we identified 1145 (24%), 904 (19%), and 1901 (40%) poor-risk patients by the IMDC, MSKCC, and Hudes models, respectively. Median overall survival was 8.5 months, 7.5 months, and 10.6 months; and median progression-free survival was 3.7 months, 3.5 months, and 4.2 months in the IMDC, MSKCC, and Hudes models, respectively. The objective response rate ranged between 10% and 14%. Additionally, 9% to 14% of poor-risk patients continued to receive treatment for > 12 months. Most importantly, the C-index was 0.826, 0.830, and 0.825 in the IMDC, MSKCC, and Hudes risk models, respectively. Conclusion: We demonstrate that poor-risk patients continue to have dismal outcomes and warrant alternative treatment strategies to help improve outcomes. A subset of patients experienced prolonged clinical benefit and should be further explored.