A phase II evaluation of aflibercept in the treatment of recurrent or persistent endometrial cancer: A Gynecologic Oncology Group study

作者：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

来源：Gynecologic Oncology, 2012, 127(3): 538-543.

DOI：10.1016/j.ygyno.2012.08.020

• Aflibercept
• Endometrial cancer
• VEGF Trap
• Toxicity
• Fibroblast growth factor

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusions. Aflibercept met pretrial activity parameters, but was associated with significant toxicity at this dose and schedule in this population.

• 出版日期2012-12