Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800).
Objectives—Atrasentan, an oral endothelin-A receptor antagonist, demonstrated Phase I activity in patients with renal cell cancer (RCC). A phase II study was undertaken in patients with measurable or bone only metastatic RCC in the pre-VEGF/TKI era.
Methods and Materials—Patients were stratified on disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0-1 prior immunotherapies, and ECOG PS 0 - 2. Patients received atrasentan 10 mg/day until progression. The primary endpoint was progressionfree (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A two-stage design was used for cohorts without prior immunotherapy.
Results—From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3 - 107 weeks). Toxicities were mild; 71% of patients reported no Grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n=3), dyspnea (n=2), thrombosis, and arrhythmia (n=1 each). Two grade 5 events (dyspnea and constitutional) were possibly treatment-related. Six-month PF rates (90% CI) were 14% (6 - 25%), 0% (0 – 39%), 8% (1 – 23%) and 22% (8 – 44%) respectively for patients with prior immunotherapy/measurable disease (n=44), prior immunotherapy/bone metastases (n=6), no prior immunotherapy/measurable disease (n=25), and no prior immunotherapy/bone metastases (n=18). Median PF survival was 2.3 months (95% CI, 2.0 – 3.5 months).
Conclusions—While well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.
Published In/Presented At
Carducci, M. A., Manola, J., Nair, S. G., Liu, G., Rousey, S., Dutcher, J. P., & Wilding, G. (2015). Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800). Clinical Genitourinary Cancer, doi:10.1016/j.clgc.2015.07.002
Medical Sciences | Medicine and Health Sciences
Department of Medicine, Hematology-Medical Oncology Division, Department of Medicine Faculty