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

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.