Coleman, Robert L., Sill, Michael W., Lankes, Heather A., Fader, Amanda Nickles, Finkler, Neil J., Hoffman, James S., Rose, Peter G., Sutton, Gregory P., Drescher, Charles W., McMeekin, D. Scott, Hu, Wei, Deavers, Michael, Godwin, Andrew K., Alpaugh, R. Katherine, Sood, Anil K.
funding text
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical and Data Center (CA 37517). This was also supported, in part, by NIH grant P50 CA098258. The following Gynecologic Oncology Group member institutions participated in this study: Duke University Medical Center, Walter Reed Army Medical Center, Northwestern Memorial Hospital, University of Washington. University of North Carolina School of Medicine, University of New Mexico, The Cleveland Clinic Foundation, Washington University School of Medicine, Columbus Cancer Council, MD Anderson Cancer Center, Fox Chase Cancer Center, University of Oklahoma, Case Western Reserve University, University of Wisconsin, The Hospital of Central Connecticut, and Community Clinical Oncology Program. RLC is supported in part by the Ann Rife Cox Chair in Gynecology. CellSearch Endothelial kits were supplied by Veridex, LLC (Huntington Valley, PA) as part of a collaborative research agreement with Fox Chase Cancer Center and Veridex. We also acknowledge Regeneron for providing the investigational drug. Dr. Robert Coleman received grant funding from Sanofi, who has entered into a business relationship with Regeneron for this compound (aflibercept). All other co-authors have no conflicts of interest to declare.
abstract
Objectives. Aflibercept targets vascular endothelial growth factor and placental growth factor. We evaluated activity and toxicity of aflibercept in recurrent/persistent endometrial cancer patients. Biomarkers and association with clinical characteristics and outcome were explored. Methods. Eligible patients had measurable disease; 1-2 prior cytotoxic regimens; performance status 0-2. Aflibercept 4 mg/kg IV q14 days (28-day cycles) was administered until disease progression or prohibitive toxicity. Primary endpoints were the proportion of patients with progression-free survival at 6 months (PFS6) and tumor response rate. A flexible two-stage group sequential design to detect 20% increases in the proportion of patients responding or enduring PFS6 with 90% power (alpha=10%) was employed. Results. Forty-nine patients were enrolled; five were excluded: wrong primary (2), second primary (1), wrong cell type (1); and never treated (1). Median age was 64 (range 48-83). Eighteen patients (41%) had two prior regimens; 27 (61%) had prior radiation. The PFS6 rate was 41%; three patients (7%, 90% Cl: 2-17) had partial response. Of note, 10 patients (23%) met the PFS6 endpoint without starting a subsequent therapy; the remaining eight patients discontinued therapy for toxicity and started another therapy before 6 months elapsed. Median PFS and overall survival were 2.9 months and 14.6 months, respectively. Significant grade 3/4 toxicities were: cardiovascular (23%/5%), constitutional (7%/0), hemorrhage (2%/5%), metabolic (7%/2%), and pain (18%/0). Two treatment-related deaths were recorded: GI perforation (1), and arterial rupture (1). FGF1 expression was associated with response. Conclusions. Aflibercept met pretrial activity parameters, but was associated with significant toxicity at this dose and schedule in this population. (C) 2012 Elsevier Inc. All rights reserved.