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

objectivesAflibercept 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.

methodsEligible 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 (α=10%) was employed.

resultsForty-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% CI: 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.

conclusionsAflibercept met pretrial activity parameters, but was associated with significant toxicity at this dose and schedule in this population.