An in-depth multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) that do not meet eligibility criteria for clinical trials.
4536 Background: Clinical trials have strict eligibility criteria that exclude many patients to whom the trial results are later extrapolated to in clinical practice. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) <70%, brain metastases, non-clear cell histology, hemoglobin<=9 g/dL, creatinine >2x the upper limit of normal, platelet count of <100x103/uL, neutrophil count <1500/mm3 or corrected calcium>=12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p<0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p=0.0074). Patients who were excluded due to KPS<70, hemoglobin<=9 g/dL, calcium >=12, brain metastases, and non-clear cell histology, had a hazard ratio (HR) for death of 2.8 (95%CI 2.4-3.4), 1.8 (95%CI 1.4-2.2), 1.8 (95%CI 1.2-2.7), 1.4 (95%CI 1.1-1.8), and 1.4 (95%CI 1.1-1.7), respectively (all p<0.01). When adjusted by the Heng et al prognostic categories, the HR for death between trial ineligible vs trial eligible patients was 1.511 (95%CI=1.335-1.710, p<0.0001). Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Specific trials addressing the needs of protocol ineligible patients and assessing OS are required. [Table: see text]