title: Aflibercept (VEGF Trap) in inoperable stage III or stage iv melanoma of cutaneous or uveal origin.
abstract: OBJECTIVE
  Aflibercept is a soluble decoy VEGF receptor and angiogenesis inhibitor with potent preclinical antitumor activity in melanoma. We conducted a multicenter phase II study in patients with inoperable stage III or IV melanoma and no prior chemotherapy.
  
  
  METHODS
  A two-stage design was adopted to evaluate 4-month progression-free survival rate (PFSR) and response rate. Aflibercept was given at 4 mg/kg intravenously every 2 weeks. Response was assessed every 8 weeks. First-stage accrual of 21 patients was specified and with an adequate 4-month PFSR accrual continued to a total of 41.
  
  
  RESULTS
  Forty-one patients of ages 23 to 84 (median = 57) were enrolled. Thirty-nine had American Joint Committee on Cancer stage IV (5 M1a, 7 M1b, and 27 M1c) and 2 had inoperable stage IIIC (N3). Eastern Cooperative Oncology Group (ECOG) performance status was 0 (27 patients) or 1 (14 patients). Ten patients had primary uveal melanoma, 28 cutaneous, and 3 had unknown primaries. A median of 7 cycles were initiated (range: 1-56). Grade 3 and 4 toxicities included hypertension in 9 patients (22%) and proteinuria in 6 (15%). Among 40 patients evaluable for efficacy (those who initiated aflibercept), 3 (7.5%) had a confirmed partial response and 20 had progression-free survival of 4 months or above. The predicted 1-year survival rate derived from the Korn meta-analysis model is 36% (N = 39), whereas we observed a corresponding 56.4% survival rate at 1 year (95% CI, 43-74, P < 0.005). Median overall survival in this trial is 16.3 months (95% CI, 9.2 to not reached). We observed a significant association between severity of hypertension following aflibercept and survival improvement.
  
  
  CONCLUSIONS
  Aflibercept showed promising activity in patients with metastatic melanoma of cutaneous or uveal origin. Further evaluation of aflibercept as a single agent and in combination is warranted.
authors: University of Pittsburgh, Pittsburgh, Pennsylvania, USA. tarhiniaa@upmc.edu
authors: Ahmad A
authors: AA
authors: Tarhini
authors: Paul
authors: P
authors: Frankel
authors: Kim A
authors: KA
authors: Margolin
authors: Scott
authors: S
authors: Christensen
authors: Christopher
authors: C
authors: Ruel
authors: Janice
authors: J
authors: Shipe-Spotloe
authors: David R
authors: DR
authors: Gandara
authors: Alice
authors: A
authors: Chen
authors: John M
authors: JM
authors: Kirkwood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor