PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

©2011 AACR.